Anaesthesia

Introduction:

Aesophagogastroduodenoscopy (EGD), is a common same-day procedure used for both diagnostic and therapeutic purposes during which a small flexible fibreoptic tubular camera is introduced through the mouth and advanced through the pharynx into the oaesophagus, stomach, and duodenum. EGD procedures are performed under deep sedation, since they can elicit significant pain, discomfort, and anxiety. When pain is not controlled properly, this can lead to an increase use of adjunctive medications such as opioids. This can extend the length of stay and increase adverse outcomes.¹ In a prospective, randomised, double-blinded study, Bedirli et al. found that use of opioid medications such as fentanyl are associated with increased adverse outcomes.²

Since procedural sedation-related complications (such as hypoxia, hypotension, desaturation, and emergent airway intervention) remain one of the biggest challenges in EGD procedures, it is important to select the correct medications to reduce these complications.³ Currently, propofol is the most common and popular main procedural sedation agent used for EGD procedures.^4,5

Propofol is the preferred main intravenous agent in EGD procedures due to its amnestic, sedative, and hypotonic properties.⁶ It has also been favoured due to its ultra-rapid response and duration of effects, usually taking 30-60 seconds for onset of action and lasting up to 4-8 minutes.⁷ However, propofol has been associated with significant adverse effects that include dose-related hypotension, bradycardia, laryngospasms, and apnoea.^8,9 Propofol does not have analgesic properties and will usually be combined with opioids for pain control.¹⁰

Ketamine is classified as a dissociative anaesthetic and is known to provide analgesia and amnesia. Important to note, it causes less respiratory or cardiovascular depression when used alone for children greater than 4 months of age.¹¹ However, ketamine alone can cause such side effects of laryngospasm, increase secretions, and vomiting.^12,13

The mixture of propofol and ketamine in one syringe (coined ketofol) has been shown to be effective in sedation for various procedures, such as spinal anaesthesia,¹⁴ along with orthopaedic¹⁵ and cardiovascular procedures¹⁶ in adults and children. Use of this combination has been favoured in brief but painful emergency room procedures due to the opposing haemodynamic and respiratory effects of both sedative medications.¹⁷ The negative cardiac effects produced by propofol can be attenuated with the use of ketamine, resulting in an increase in mean arterial pressures and cardiac indices.^18,19 The complementary effect of both mediations has enabled the use of lower doses for each medication, thus lowering the toxicity and side effects.^20,21 Although there are studies comparing activities of ketofol sedations,^22-25 there has not been a study published on ketofol compared to propofol use in children during EGD procedures.

The primary goal of this study was to determine if there were differences in the outcomes of adverse cardiac and pulmonary events, vital sign parameters including objective pain, and administration of adjunct pain medication (for which fentanyl was used in this study) during EGD procedures between propofol and ketofol groups. A secondary goal was to determine if there was a difference in site performance metrics for EGD procedures (sedation time, stop of sedation to discharge time, and length of stay) between propofol and ketofol groups.

Methods:

This study protocol was approved by the Naval Medical Center Portsmouth Institutional Review Board in compliance with all applicable federal regulations governing the protection of human subjects. Research data was derived from an approved IRB protocol: number NMCP.2018.0021. Written informed consent was not required by the Naval Medical Center Portsmouth IRB, as this data concerned historical dae-identified patients.

Study Design

This was a single centre, retrospective study of a cohort of children (ranging from 2 to 18 years). Data was collected from March 2011 to September 2013 at Naval Medical Center Portsmouth’s Paediatric Sedation Centre. EGD and sedation protocol was not changed during this time period. EGD procedures were performed by the same paediatric gastroenterologists throughout this time period. Sedation was performed by the same paediatric intensivists throughout this time period. All patients used in this study were involved in a same day EGD procedure. Forty-one patients underwent deep sedation via propofol as main sedation agent from March 2011 to May 2012. Forty-nine patients underwent deep sedation via propofol and ketamine combination as main sedation agent from May 2012 to September 2013. Each main sedation agent was given in a similar fashion as an initial intravenous loading dose based on 1 mg/kg propofol followed by an intravenous infusion of 200-250 mcg/kg/minute that was started less than 10 minutes prior to start of the procedure and stopped at the end of the procedure. Ketofol solution used was a 1:5 ratio of ketamine to propofol (40 mg:200 mg). One mcg/kg of fentanyl was given when the sedationist during the EGD perceived the patient experiencing pain. Exclusion criteria included: patients less than 2 years and greater than 18 years, those less than 10 kg, and patients receiving adjunct medications other than fentanyl, ondansetron, or lidocaine.

Data Collection

Fourteen patients were excluded due to weight less than or equal to 10 kg. In addition, 12 patients were excluded due to age less than 2 years or greater than 18 years. Past medical history, ASA class, procedure indications, age, weight, sex, pain scores, vital signs (mean arterial blood pressure [MAP], heart rate [HR], and respiratory rate [RR]), unplanned events (hypoxia defined as SPO2 less than 85% at any time point, and hypotension defined as mean arterial blood pressure with greater than 20% decrease from baseline blood pressure), emergent airway intervention (defined as apnoea needing bag mask ventilation or CPAP use), and unplanned intubation. Vitals and pain scores were obtained from initial presentation in the sedation suite, start of procedure, every 5 minutes during the procedure to stop of sedation, and at time of discharge. Midway procedure vitals used for statistical analysis were obtained by selecting vitals that were at the half-way point of the patient’s EGD procedure. The Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS) was performed every 5 minutes during the EGD procedure by an independent United States Navy Corpsman and used to evaluate patient’s pain prior, during, at stop of sedation, and after procedure for this study.²⁶

Statistics

All statistics performed in this study were calculated using SPSS Statistics programme (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.). Mann-Whitney U nonparametric test between independent groups was performed to compare age, weight, total EGD procedure time, total time of sedation during EGD procedure, time from stop of sedation to discharge, total length of stay, and total fentanyl use (in mcg/kg) between the two main groups in this study (propofol and ketofol group). The significance level was set to 0.008 after a Bonferroni was corrected, in order to address the probability of making one or more false discoveries when performing multiple hypotheses tests. A repeated measures ANOVA was run to determine the effect of treatments over time for HR, MAP, and RR. Mauchly's test of sphericity was performed for both age groups. The Fisher Exact test was performed to compare propofol to ketofol in unplanned hypotensive events and unplanned apnoea requiring bag valve mask or CPAP. Pearson Correlation statistics were performed to study possible correlations between propofol or fentanyl and sedation time or length of stay. Statistical significance for Pearson Correlation statistics was considered when two-tailed p<0.001.

Results:

Table 1. Demographic divided into 2 age groups. EE= eosinophilic esophagitis. * indicates statistically significant difference.

Figure 1. Propofol amount total per weight (mg/kg). Bars represent standard error of the mean. There was no significant difference between the propofol and ketofol in all age groups.

Figure 2. Fentanyl amount total per weight (mcg/kg). Bars represent standard error of the mean. In all age groups, there was a significant difference between propofol and ketofol. *p<.008.

Figure 3. Vital signs. Mean arterial pressures for ages A) 2-11 years and B) 12-18 years. Main sedative agents’ MAPs were statistically different for ages 2-11 years (p =0.004), but not for ages 12-18 years (p =0.224) for all time periods. Heart rate for ages C) 2-11 years and D) 12-18 years. For Heart Rate, there was a statistically significant interaction between treatment and time for both age group using the Greenhouse-Geisser correction, p =0.002, p =0.014. Main sedative agents’ HRs showed to be statistically different for both age groups, p <0.001 and p =0.004.

Figure 4. Duration of time. A) total sedation time, B) stop of sedation to discharge, and C) total length of stay. In all age groups, there was no significant difference between propofol and ketofol. Bars represent standard error of the mean. *p<0.008.

Figure 5. Pearson Correlation. Propofol versus total sedation time for ages A) 2-11 years (p<0.01*), and B) 12-18 years (p<0.01*). Propofol versus length of stay for ages C) 2-11 years (p<0.01*), and D) 12-18 years (p<0.01*). * Correlation is significant at the 0.01 level (2-tailed).

Figure 6. Pearson Correlation. Fentanyl versus total sedation time for ages A) 2-11 years (p=0.506), and B) 12-18 years (p=0.961). Fentanyl versus length of stay for ages C) 2-11 years (p=0.378), and D) 12-18 years (p=0.352). No significant correlation was not seen for all age groups.

Ninety patients were retrospectively analysed in this study. Baseline demographics were similar between the groups, except for gender proportions (Table 1). Similar amounts of propofol per weight were used in each group (Figure 1). Ketofol significantly reduced fentanyl use in all age groups by ≥.99 mcg/kg compared to propofol alone (p<0.008 for all age groups, Figure 2). In the 2-11 year old age group, the propofol group required a mean fentanyl dose of 1.96 mcg/kg ± 1.24 mcg/kg and the ketofol group required a mean fentanyl dose of 0.44 mcg/kg ± 0.49 mcg/kg; thus ketofol required about 1.52 mcg/kg less fentanyl during EGD procedures. In the 12-18 year old group, the propofol group required a mean fentanyl dose of 1.38 mcg/kg ± 1.05 mcg/kg and the ketofol group required a mean fentanyl dose of 0.39 mcg/kg ± 0.59 mcg/kg; thus ketofol required about 1 mcg/kg less fentanyl during EGD procedures.

Vital signs (HR, RR, and MAP) and CHEOPS pain scores were obtained and analysed for baseline vitals, at the procedure midpoint, at stop of sedation, and at time of discharge. CHEOPS pain scores’ mean was 6 throughout all time periods for both groups, thus there was no statistically significant difference.

A repeated measures ANOVA was run to determine the effect of treatments over time for RR. There was sphericity for the interaction term, as assessed by Mauchly's test of sphericity in both age groups (p =0.070, p =0.762). For RR, there was not a statistically significant interaction between treatment and time for both age groups, p =0.163, p =0.804. The treatments were not found to be statistically different for either age group, p =0.736 and p =0.224.

A repeated measures ANOVA was run to determine the effect of treatments over time for HR. As assessed by Mauchly's test of sphericity, no sphericity was found in either age group (p <0.05). For HR, using the Greenhouse-Geisser correction, a statistically significant interaction was found between treatment and time for both age group, p =0.002, p =0.014. The treatments were found to be statistically different for both age groups, p <0.001 and p =0.004. A repeated measures ANOVA was run to determine the effect of treatments over time for MAP. Sphericity was found in both age groups for the interaction term, as assessed by Mauchly's test of sphericity (p =0.209, p =0.269). For MAP, there was not a statistically significant interaction between treatment and time for either age group, p =0.261, p =0.591. The treatments were statistically different for the 2-11 year old group (p=0.004), but not statistically different for the 12-18 year old group (p=0.224). (Figure 3 A-D)

Unplanned events were analysed for clinically significant hypoxia, hypotension, emergent airway intervention, and unplanned intubations. Ketofol compared to propofol had fewer hypotensive events in the 2-11 year old age group (3.7% versus 15.4%, p=0.192) and in the 12-18 year old age group (0% versus 13.3%, p=0.144). Ketofol compared to propofol had statistically significant fewer apnoea events requiring bag valve mask or CPAP intervention for the 2-11 year old group (3.7% versus 53.8%, p<0.001) and for the 12-18 year old group (0% versus 33.3%, p=0.005). There were no significant hypoxia events. There was one unplanned intubation in the propofol group of a healthy ASA I twelve year old female who had a 20 mL emesis episode after a loading dose of propofol was given on induction. (Table 1)

With propofol leading to significantly more fentanyl usage, more hypotension and emergent airway intervention during EGD procedures, we performed analysis to see if there was an effect on sedation time, time from stop of sedation to discharge, and length of stay (LOS). In all age groups, there was no statistical difference between propofol and ketofol for sedation time (p=0.115 for ages 2-11 years, p=0.124 for ages 12-18 years), time from stop of sedation to discharge (p=0.033 for ages 2-11 years, p=0.511 for ages 12-18 years), and LOS (p=0.026 for ages 2-11 years, p=0.109 for ages 12-18 years) (Figure 4). Based on Pearson correlation test, it was established that propofol was positively correlated with sedation time and LOS (+0.753 for sedation time and +0.611 correlation for length of stay with <0.001 significance) (Figure 5). There was no significant correlation between fentanyl and sedation time or LOS (Figure 6).

Discussion:

This was a retrospective study looking at 90 paediatric patients, ages 2-18 years, undergoing EGD procedures with either propofol or ketofol as the main sedative medication. Patients in this study had similar weights, ages, ASA scores, and EGD indications; however there baseline demographics were not similar with regards to gender proportion (Table 1). Based on the large prospective database on sedation use for procedures outside the operating room obtained by the Paediatric Sedation Research Consortium,²⁷ we separated our patient population into two age risk groups to allow our results to be generalisable. To our knowledge, this study is the first to show that ketofol, when compared to propofol, significantly reduces fentanyl use (≥.99 mcg/kg, Figure 2) and cardiopulmonary adverse outcomes (Table 1) in paediatric EGD procedures.

EGD procedures are known to be invasive and painful. To decrease the pain appreciated by a patient, various adjuncts are often utilised. In our study, we used fentanyl for adjunct pain control. In both main sedation medication groups (propofol and ketofol), there was no statistical significance seen in objective pain based on CHEOPS scores with a mean score of 6 in all age groups (p>0.05). However, the amount of adjunct needed to maintain adequate pain control between both groups statistically and clinically differed (Figure 2). In all age groups, the propofol group compared to the ketofol group required almost 1 mcg/kg more of fentanyl, which leads to the potential for the patient to experience higher incidence of side effects, such as respiratory depression and hypoxia.^28-30

The mechanism that lead to this significant difference in opioid demand between ketofol and propofol is most likely due to ketamine’s ability to stimulate opioid sigma receptors,31 thus leading to opioid sparing effects. It is unclear if propofol and ketamine interaction heightens this opioid sparing effect, because ketamine alone has not been shown to lead to opioid sparing effects in children.³²

In a review of our population’s vital signs, there was a significantly higher MAP in the ketofol group compared to the propofol group for ages 2 to 18 years (Figure 3 A-B). In addition, the ketofol group had statistically higher HR compared to the propofol group for ages 2 to 18 years (Figure 3 C-D). It is our thought that this increase in MAP and HR in the ketofol group mediated by ketamine is a protective factor against major hypotensive changes (31). It is this effect that minimised unplanned hypotensive events in our ketofol group compared to the propofol group by 11.7% in ages 2-11 years and 13.3% in ages 12-18 years (Table 1).

One of the more noticeable differences in our main sedative medication groups was the unplanned apnoea events requiring CPAP or bag mask ventilation intervention. In our 2 to 11 year age group, propofol had 50.1% more apnoea events needing intervention compared to ketofol. In our 12 to 18 year old group, propofol had 33.3% more apnoea events needing respiratory intervention compared to ketofol. This was found to be statistically significant. It is unclear if this is also clinically significant since no emergent airway intubation was needed for these events. However, there was 1 emergent airway intubation in the 12-18 year old propofol group. Based on the review of the medical records, it appears that these apnoea events needing respiratory intervention were mostly associated after the initial loading dose of either propofol or ketofol prior to or at the start of the infusion. Thus, bring into question if not starting with a loading dose bolus would decrease adverse effects.

Despite the propofol group requiring more respiratory intervention, increased fentanyl use, and less haemodynamic stability seen, there was no statistical differences in total sedation time and LOS between the two main sedation medication groups (Figure 4). Yet when we ran correlation statistics, there was a positive correlation to increased propofol dosages, total sedation time, and LOS in ages 2 to 18 years (Figure 5); therefore, if our procedures were longer, there could be a statistically and possibly clinically significant increase in total sedation time and LOS for the propofol only group. Thus, we can infer that propofol compared to ketofol is not the main sedation medication of choice for longer similarly painful procedures in children ages 2 to 18 years, such as EGD procedure followed by a colonoscopy.

A limitation of our study is that it is retrospective. With that, we were not able to blind our sedationists to the main sedation medication that was chosen and could not control the interventions that were performed. Yet, based on strict exclusion criteria, we were able to control the interventions used in our analysis. Also, in our study we did not analyse patients under the age of 2 years. Reviewing the data, we had seven patients, and thus this patient population size was not powered to perform the proper statistical analysis. Another limitation to consider is the time difference in procedure protocols. However, since this study included over 2 years of data, procedure protocols were the same. Additionally, the EGD indications were similar between ketofol and propofol (Table 1). Another consideration of this study is generalisability. This study was conducted at a single centre, but the way we analysed our results makes it easier to perform large scale prospective studies to further investigate our findings. Last limitation is directly correlating fentanyl dose with a significant adverse event. Due to the short length of the EGD procedure, constant sedation medication infusion, and fentanyl dose, it is difficult to directly say that a particular fentanyl dose alone leads to an adverse event. Therefore we can only speculate based on correlation.

Conclusions:

Our study found that ketofol significantly reduced fentanyl use in all age groups by ≥0.99 mcg/kg and cardiopulmonary adverse events compared to propofol alone. In addition, an increase in the amount of propofol was positively correlated to increasing LOS and total sedation time for a child undergoing an EGD procedure. This suggests that increasing amounts of propofol leads to greater LOS. To conclude, our study indicates that ketofol can be a safer alternative to propofol use alone for deep sedation in EGD procedures for children ages 2 to 18 years.

Introduction

Epidural anaesthesia is one of the favored and effective treatment options for labour pain. It is usually safe and only a handful situations lead to absolute contraindications to this technique such as patient’s refusal, lack of expertise and equipment, severe coagulopathy and infection at the site of puncture (1). However, as with any other technique and procedure, epidural anaesthesia is not flawless. The side effects and complications include hypotension, pruritus, inadequate analgesia, post puncture headache, nerve damage, infection, and epidural haematoma (1,2). Headache is common in one third of the patients after lumbar puncture however, the frequency is less in epidural anaesthesia as the fluid is injected in and not removed in the latter (3). Accidental dural damage and subsequent headache following epidural anaesthesia is uncommon and is an important cause of morbidity which can limit patient severely. Further, in rarest of rare cases Pneumocephalus can develop after epidural anaesthesia which has rarely been reported. We report a patient who developed Pneumocephalus after receiving epidural anaesthesia for labour pain.

Case Report:

A 39 year old female presented to our Emergency Department with severe headache not responsive to analgesics. The headache started developing 10 to 12 hours after she was given an epidural which was attempted three times for labour pain which was four days prior at a nearby medical center . The severity of the headache did not change with lying or the upright position. She had no symptoms of vomiting, no fever and no confusion. Neurological examination and vital signs were unremarkable. The site of the spinal anaesthesia did not reveal any swelling or any signs of infection. An urgent head CT scan was performed which revealed Pneumocephalus denoted by numerous left fronto-parietal extra axial air locules (Figure 1 and Figure 2). MRI spine revealed mild subcutaneous oedema at the site of the needle insertion without any haemorrhage or collection. The patient was admitted and treated conservatively for six days and follow up serial head CT scans showed complete resorption of the Pneumocephalus and the patient’s symptoms resolved completely. The patient was discharged and the follow up was uneventful.

Figure 1: Pneumocephalus seen as locules of air (black color) in the left fronto-parietal region denoted by arrows (Axial section)

Figure 2: Multiple pockets of air seen in the Saggital section marked by arrows demonstrate the Pneumocephalus.

Discussion:

Pneumocephalus is the presence of air in the intracranial cavity. It can be acute ( less than72 hours ) or delayed (more than 72 hours). The most common site is the frontal region (4). Plain skull x-rays can detect Pneumocephalus of about 2 ml, whereas it requires only 0.5 ml of air to be detected by a CT scan (5). Pneumocephalus is most commonly a result of traumatic brain injury, surgical intervention of the brain or infection (5). Trauma accounts for up to 75% percent of the total cases. Chronic infections of ENT especially otitis media also amounts to a number of significant cases. Surgical procedures of brain, spine and ENT like sinus surgery, nasal polypectomy and nasal septum resection accounts for the causes. The incidence after supratentorial craniotomy has been reported to be 100% (6, 7). However, it is very unusual for pneumocephalus to develop post epidural anaeasthesia possibly due to ball valve mechanism in which the air enters the space through the CSF leakage which allows input but not output. Headache post lumbar puncture and epidural anaesthesia is relatively not uncommon but certain situations may demand a more thoughtful approach (3).

In our patient we suspect there was a puncture of the dura during epidural anaesthesia which led to air being trapped and siphoned upwards in an inverted soda bottle fashion. This is supported by the meta-analysis done by Choi et al. which states the incidence of accidental dural puncture in epidural insertion to be 1.5% and among those 52 % will have post puncture headaches (8). In another extensive study performed over ten years, the overall incidence of accidental dural puncture and postdural puncture headache were 0.32% and 0.38%, respectively (9). The authors further stressed that if more than one attempt was required to identify the epidural space, the accidental dural puncture rate increased to 0.91%. In our patient we witnessed the same wherein three attempts were made to identify the epidural space which increased the risk of dural injury and subsequent leaking. Pneumocephalus usually gets absorbed without any clinical manifestations. The conservative treatment involves placing the patient at rest, avoiding Valsalva manoeuver, administering analgesics. With these measures, reabsorption was observed in 85% of cases after 2–3 weeks (5). Use of oxygen mask, nasal catheter, hyperbaric oxygen sessions and good hydration have also been reported. If conservative measures fail to provide the desired results then specific treatment like a epidural blood patch or even surgical closure of the dural gap is indicated (3, 10).

Introduction

Hypertension is the most common risk factor for perioperative cardiovascular emergencies. Acute episodes of hypertension may arise due to the aggravation of a pre-existing chronic hypertensive condition or as de novo phenomena¹.

Emergency, anaesthesia, intensive care and surgery are among the clinical settings where proper recognition and management of acute hypertensive episodes is of great importance. Many surgical events may induce sympathetic activity, leading to sudden elevations in BP².

The long term end-organ effects add to patient morbidity and mortality. Ensuring cardiovascular stability and pre-optimization of BP allows safe manipulation of physiology and pharmacology during anaesthesia². Different medications are available for the management of hypertensive emergencies. The greatest challenge is the acute care setting where the need for proper and sustained control of BP exists.

Definition

Acute severe elevations in BP have several terms. The syndrome characterized by a sudden increase in systolic and diastolic BPs (equal to or greater than 180/120 mmHg) associated with acute end-organ damage that requires immediate management otherwise it might be life-threatening was defined as malignant hypertension³. The international blood pressure control guidelines removed this term and replaced it with hypertensive emergency or crisis⁴.  

Criteria for hypertensive emergencies (crises) include: dissecting aortic aneurysm, acute left ventricular failure with pulmonary oedema, acute myocardial ischemia, eclampsia, acute renal failure, symptomatic microangiopathic haemolytic anemia and hypertensive encephalopathy⁵.

While they suggest 'hypertensive urgency' for patients with severe hypertension without acute end-organ damage³.  The difference between hypertensive emergencies and urgencies depends on the existence of acute organ damage, rather than the absolute level of blood pressure⁵.

Causes of hypertensive crises

Cessation of antihypertensive medications is one of the main causes. Other common causes are autonomic hyperactivity, collagen-vascular diseases, drug use (stimulants, e.g. amphetamines and cocaine), glomerulonephritis, head trauma, pre-eclampsia and eclampsia, and renovascular hypertension⁶.

Signs and symptoms of hypertensive crisisinclude severe chest pain, severe headache accompanied by confusion and blurred vision, nausea and vomiting, severe anxiety, shortness of breath, seizures and unresponsiveness.

Pathogenesis

Humoral vasoconstrictors released in the hypertensive crises episodes result in a sudden increase in systemic vascular resistance. Endothelial injury accompanies severe elevations of BP resulting in fibrinoid necrosis of the arterioles with the deposition of platelets and fibrin, and a breakdown of the normal autoregulatory function. The resulting ischemia speeds the further release of vasoactive substances completing a vicious cycle⁷.

Perioperative hypertension

At least 25% of hypertensive patients who undergo noncardiac surgery develop myocardial ischemia associated with the induction of anaesthesia or during the intraoperative or early post-anaesthesia period⁸. Previous history of diastolic hypertension greater than 110 mmHg is a common predictor of perioperative hypertension. The level of risk depends on the severity of hypertension⁹.

Sympathetic activation during the induction of anaesthesia increases the BP by 20 to 30 mmHg and the heart rate by 15 to 20 beats per minute in normotensive individuals⁸. These responses may be more obvious in patients with untreated hypertension in whom the systolic BP can increase by 90 mmHg and heart rate by 40 beats per minute.

Intraoperative hypertension is associated with acute pain induced sympathetic stimulation besides certain types of surgical procedures like carotid surgery, intrathoracic surgery and abdominal aortic surgery. Paix et al, analysed 70 incidents of intraoperative hypertension and reported that drugs were the precipitating cause (inadvertent vasopressor administration by the anaesthetist or surgeon, intravenous adrenaline with local anaesthetic and failure to deliver a volatile agent or nitrous oxide) in 59% of the cases. Light anaesthesia and excessive surgical stimulation represented 21% of incidents, while equipment related causes (ventilation problems e.g. stuck valve, hypoventilation, soda lime exhaustion and endobronchial intubation) were 13% of incidents. Awareness under general anaesthesia, myocardial infarction and pulmonary oedema represented 7% of incidents¹⁰.

In the early postanaesthesia period, hypertension often starts within 10 to 20 minutes after surgery and may persist for 4 hours. Besides pain induced sympathetic stimulation, hypoxia, intravascular volume overload from excessive intraoperative fluid therapy and hypothermia can promote postoperative hypertension. If untreated, patients are at high risk for myocardial ischemia, cerebrovascular accidents and bleeding¹¹. Hypertension might happen 24 to 48 hours postoperative due to fluid mobilisation from the extravascular space, besides cessation of antihypertensive medication in the early postoperative period¹².

The absolute level of BP is as important as the rate of increase. For example, patients with chronic hypertension may tolerate systolic BPs (SBP) of 200 mm Hg without developing hypertensive encephalopathy, while pregnant women and children may develop encephalopathy with diastolic BPs of 100 mm Hg¹³.

Preoperative general considerations for hypertensive patients

During preoperative assessment we have to review associated medical problems such as ischaemic heart disease, cerebrovascular disease and renal failure. This can assess the risk for anaesthesia and so the hypertensive end-organ damage. Some patients with hypertension are asymptomatic and accidentally discovered during preoperative assessment. Incidental hypertension may suggest long standing hypertensive disease¹. Idiopathic hypertension comprises about ninety percent of hypertensive patients⁶.

Management of perioperative hypertension crises

The treatment plan of perioperative hypertension differs from treatment of chronic hypertension. Hypertensive patients undergoing elective surgery are at risk for increased perioperative hypertensive attacks. Postponement of elective surgery is recommended in chronic hypertensive patients if the diastolic BP is ≥110 mm Hg until the BP is controlled¹⁴. We have to determine if it is a hypertensive emergency or urgency, besides the underlying causes of the patient’s BP elevation.

The most appropriate medication for management of hypertensive emergency should have a rapid onset of action, a short duration of action, be rapidly titratable, allow for dosage adjustment, have a low incidence of toxicity, be well tolerated and have few contraindications^2,15. A parenteral antihypertensive agent is preferred due to rapid onset of action and ease of titration⁵.

The goal of therapy is to halt the vascular damage and reverse the pathological process, not to normalise the BP. Guidelines by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High BP for treating hypertensive emergencies include starting intervention with reducing systolic BP by 10 to 15%, up to 25% within the first hour. Followed

by gradual reduction of the absolute BP to 160/110 mmHg over the following two to six hours^5,16.

Hypertension that occurs with tracheal intubation, surgical incision and emergence from anaesthesia is best treated with short-acting β-blockers, calcium channel blockers, vasodilators, or angiotensin-converting enzyme inhibitors. Postoperative hypertension is best managed by correction of precipitating factors (pain, hypothermia, hypervolemia, hypoxia and hypercarbia)¹⁷.

Unintentional hypotension and associated organ hypoperfusion happens with aggressive attempts to lower BP since the homeostatic mechanisms depend on higher blood pressure for adequate organ perfusion. While inadequate lowering of BP may result in increased morbidity and mortality. However, the alteration between overshooting BP and severe hypotensive states and using vasopressors to get the normotensive levels may damage end-organs and the vasculature - precise control of BP in a hypertensive crisis is a challenge¹⁸.

Since chronic hypertension shifts cerebral and renal perfusion autoregulation to a higher level, the brain and kidneys are prone to hypoperfusion with rapid decrease in blood pressure. So control of blood pressure to baseline levels should take 24 to 48 hours⁵.

In cases of aortic dissection, the systolic BP should be reduced to less than 120 mmHg within twenty minutes. In ischemic stroke, BP must be lowered to less than 185/110 before administration of thrombolytic therapy¹⁹. Gentle volume expansion with intravenous saline solution will maintain organ perfusion and prevent sudden drop in BP with using antihypertensive medications⁵. Preoperative hypertension is a hypertensive urgency, not an emergency, as it rarely involves end-organ damage with adequate time to reduce the BP¹⁸.  Longer acting oral medications such as Labetalol and Clonidine may be more suitable ²⁰. 

Common antihypertensive medications used in hypertensive crises

Sodium Nitroprusside is a combined venous and arterial vasodilator which decreases both afterload and preload. The onset of action is within seconds and duration of action lasts for one to two minutes, so continuous BP measurement is recommended. If the infusion is stopped, the BP rises immediately and returns to the pretreatment level within one to ten minutes. Prolonged intravenous administration with infusion rates more than 2 mcg/Kg/min may result in cyanide poisoning. Thus, infusion rates greater than 10 mcg/Kg/min should not be continued for prolonged periods²¹. 

Labetalol, an alpha- and beta-blocking agent has proven to be beneficial to treat patients with hypertensive emergencies. Labetalol is preferred in patients with acute dissection and patients with end-stage renal disease. The onset of action is five minutes and lasts for four to six hours. The rapid fall in BP results from a decrease in peripheral vascular resistance and a slight fall in cardiac output²².  A reasonable administration protocol is to give an initial intravenous bolus of Labetalol 0.25 mg/Kg, followed by boluses (0.5 mg/Kg) every 15 minutes until BP control or a total dose 3.25 mg/Kg. Once an adequate BP level is achieved, we can start oral therapy with gradual weaning from parenteral agents²². 

Fenoldopam, a peripheral dopamine-1-receptor agonist, induces peripheral vasodilation; administered by intravenous infusion. Duration of action from 30 to 60 minutes. Gradual decrease in blood pressure to pretreatment values occurs without rebound once the infusion is stopped because of short elimination half-life. A starting dose of 0.1 μg/kg/min, titrated by 0.05 to 0.1 μg/kg/min up to 1.6 μg/kg/min. Fenoldopam provides rapid decline in blood pressure with reflex tachycardia so beware in patients at risk of myocardial ischemia²³. 

Clevidipine, a dihydropyridine calcium channel blocker, produces rapid and precise BP reduction. It has a short half-life of about one to two minutes with potent arterial vasodilation without affecting venous capacitance, myocardial contractility or causing reflex tachycardia²⁴.  Start intravenous infusion of Clevidipine at 1-2 mg/h; titrate the dose at short intervals (90s) initially by doubling the dose. Systolic pressure decreases by at least 15% from baseline within 6 minutes post-infusion²⁴.  A 1-2 mg/h increase in infusion rate produces an additional 2-4 mmHg reduction in SBP¹⁴.  Clevidipine is an ideal agent to manage acute severe hypertension moreover safe for patients with hepatic and renal dysfunction². 

Rational approach to the management of hypertensive crises

Neurological emergencies

Subarachnoid haemorrhage, acute intracerebral haemorrhage, hypertensive encephalopathy, and acute ischemic stroke require rapid BP reduction. In hypertensive encephalopathy, reduce the mean arterial pressure (MAP) 25% over 8 hours. Labetalol, Nicardipine and Esmolol are the preferred medications; Nitroprusside and Hydralazine should be avoided²⁵. 

For acute ischemic stroke, the preferred medications are Labetalol and Nicardipine. The target BP is < 185/110 mm Hg especially if the patient is receiving fibrinolysis²⁵. 

In acute intracerebral haemorrhage, Labetalol, Nicardipine and Esmolol are preferred; avoid Nitroprusside and Hydralazine. If signs of increased intracranial pressure (ICP) exist, keep SBP < 180 mm Hg, while maintain SBP < 160 mm Hg in patients without increased ICP for the first 24 hours after onset of symptoms²⁵.  Early intensive BP control is recommended to reduce hematoma growth^26,27.   

In subarachnoid haemorrhage, Nicardipine, Labetalol and Esmolol are also the preferred agents; while Nitroprusside and Hydralazine should be avoided. Maintain the SBP < 160 mm Hg until the aneurysm is treated or cerebral vasospasm happens²⁵. 

Cardiovascular emergencies

Rapid BP reduction is also indicated in cardiovascular emergencies such as aortic dissection, acute heart failure, and acute coronary syndrome. Labetalol, Nicardipine, Nitroprusside (with beta-blocker), Esmolol, and Morphine are preferred in aortic dissection. Beta-blockers should be avoided if there is aortic valvular regurgitation or suspected cardiac tamponade. Keep the SBP   < 110 mmHg unless signs of end-organ hypoperfusion exists²⁸.  

In acute coronary syndrome if the BP is >160/100 mm Hg, Nitroglycerin and beta blockers are used to lower the BP by 20-30% of baseline but, thrombolytics are avoided if the BP is >185/100 mm Hg²⁸.  In acute heart failure use intravenous Nitroglycerin and intravenous Enalaprilat. Give vasodilators (besides diuretics) when SBP is 140 mm Hg²⁸.  

Cocaine toxicity/Pheochromocytoma

Diazepam, Phentolamine and Nitroglycerin/Nitroprusside are the preferred drugs. In cocaine toxicity, tachycardia and hypertension rarely require specific treatment. Phentolamine is proper for cocaine-associated acute coronary syndromes. In pheochromocytoma, beta blockers can be added after alpha blockade for BP control²⁹.  

Pre-eclampsia/eclampsia

The proper medications are Hydralazine, Nifedipine and Labetalol however avoid Nitroprusside, Esmolol and angiotensin-converting enzyme inhibitors. The BP should be <160/110 mm Hg in the antepartum period and during delivery. The BP should be maintained below 150/100 mm Hg if the platelet count is less than 100,000 cells mm³. Intravenous Magnesium Sulphate should also be used to prevent seizures³⁰.  

Perioperative hypertension

Nitroprusside, Nitroglycerin and Esmolol are used. Target the perioperative BP to within 20% of the patient's baseline pressure. Perioperative beta blockers are best to use in patients undergoing vascular procedures or at risk of cardiac complications²⁸.  

CONCLUSION

Perioperative hypertension commonly occurs in patients undergoing surgery. The permitted value is based on the patient’s preoperative BP. It is approximately 10% above that baseline however more reduction in BP may be warranted for patients at high risk of bleeding or with severe cardiac problems. Accurate adjustment of treatment and monitoring of patient’s response to therapy are essential to safe and effective management of perioperative hypertension.  

Introduction

The NHS is supplied with approximately 300 000 NG tubes per year¹. There are approximately 800-1000 incidents reported to the NPSA every year related to the insertion and use of NG tubes. Difficulties are often encountered with their insertion, especially in the setting of general anaesthesia. Whilst stridor and injury related to the use of NG tubes has been previously reported^2,3, it has been related to prolonged siting. We describe a case acute stridor occurring in the recovery room due to direct trauma of the airway upon NG tube insertion.

Case report

A 61-year-old male presented with clinical symptoms of bowel obstruction. His medical history included atrial fibrillation (AF) treated with flecainide, and a 30-pack year smoking history. He was previously independent with a World Health Organisation performance status of 0. After CT confirmation of bowel obstruction, he was scheduled for an emergency laparotomy. A predicted P-Possum 30 day mortality was calculated at over 10%. He required no organ support pre-operatively, although his AF was poorly controlled. He had a low thoracic epidural sited awake, followed by induction of general anaesthesia with a rapid sequence induction. An arterial line, a central venous line, and an NG tube were inserted once anaesthetised. The NG tube was documented as difficult to site, and there were several attempts at a blind insertion via the oral and nasal route, before successfully inserting under direct vision using a laryngoscope.

The operative finding was that of an unresectable caecal tumour, and a defunctioning loop colostomy was formed. The total duration was 150 minutes. Following peripheral nerve stimulation and administration of 2mg/kg Sugammadex, he was woken, extubated and escorted to recovery.

Within minutes of being in the recovery area, he was acutely stridulous. Emergency assistance was called, and after assessment he was given nebulized adrenaline (1mg diluted in 4mls 0.9% saline), and 200mg of intravenous hydrocortisone. The nasogastric tube was removed, and his breathing was then supported with CPAP via a Mapleson C circuit and 100% oxygen. Direct examination of his airway, and indirect nasendoscopy with a Storz fibre-optic scope were performed. Significant bruising of his soft palate was seen, in addition to bruising and oedema of the soft tissues around the arytenoid cartilages with a small haematoma within the valleculae [Figure 1]. After approximately twenty minutes his stridor settled.

He was transferred to a level 2 high dependency unit later that day. He did not suffer from any further airway compromise, and his symptoms completely resolved.

Discussion

The insertion of an NG tube, whilst often deemed low risk, may result in life threatening consequences⁴. There even exists a “NG tube syndrome” ⁵, the pathophysiological mechanism of which is thought to be paresis of the posterior cricoarytenoid muscles secondary to ulceration and infection over the posterior lamina of the cricoid. There is no doubt that insertion of an NG tube in the anaesthetised patient can prove to be difficult, with a failure rate of up to 50% on first pass⁶, with repeated attempts at insertion being required. However, this case highlights the need for a controlled and ordered approach to managing the difficulties that can be encountered. Medical training incorporates NG insertion as a basic skill within the curriculum, but this affords new anaesthetic trainees little help with the anaesthetised and intubated patient.

There are several techniques described to insert NG tubes in anaesthetised, intubated patients⁷. There is evidence to suggest that modified techniques such as a reverse Sellick’s manoeuvre or neck flexion with lateral pressure are better than blind insertion in the neutral position. In the right hands, insertion under direct vision can overcome most difficulties, but is again not without risk.

We feel it is important to remember that NG insertion can cause patient harm, and potentially lead to life threatening consequences. Whatever the approach or technique that is chosen, having a logical and ordered approach is paramount. Using suitable alternative methods for insertion, or abandoning the procedure, as opposed to blindly continuing to repeat the same unsuccessful method must be key for success, as would be the case for approaching any clinical encounter.

Published with the written consent of the patient.

Case

A 74 year old female presented to the A&E department after waking with a swollen tongue. She called for an ambulance and the paramedic crew initially treated her for an allergic reaction with 200mg hydrocortisone IV, 20mg chlorphenamine IV and four doses of 0.5mg adrenaline 1 in 1,000 IM. She did not improve and was transferred to the local A&E.

In A&E, she was initially stable with no stridor or difficulty in breathing but noticeably swollen tongue. Saturations were 98% on 5L nasal O₂. Blood pressure was stable at 135/75 mmHg. GCS was 15/15, but the patient was agitated from not being able to speak or retract the tongue. No further history was taken other than an allergy to shellfish, with no recent exposure. An obese habitus was noted.

A&E doctors called the anaesthetic on-call team, and on their request called the on-call ICU consultant and the on-call ENT consultant. Further adrenaline 100mcg IV, hydrocortisone 200mg IV and chlorphenamine 10mg IV were given. An attempt to look inside the mouth with a tongue depressor and torch was made by the anaesthetics/ICU team and it was quickly realised that the swelling continued into the mouth and larynx and was rapidly progressing. Given the lack of suitable equipment and the severity of the case, a decision was made to transfer to emergency theatres.

Once in emergency theatres, the on-call ENT consultant was scrubbed and ready. 100% oxygen via facemask and routine monitoring was instituted. At the request of the ENT consultant, a micro-tracheostomy was attempted with local anaesthesia but failed to pass into the trachea given the patient’s habitus. The ENT surgeons attempted an awake tracheostomy, but this was difficult due to her being agitated and unable to lie still, and a calcified trachea.

The rapidly progressing swelling compromised oxygen delivery to the lungs and the saturations began to drop quickly. The patient became bradycardic and lost consciousness. At this point, it became easier to attempt the tracheostomy. The ALS protocol was followed and CPR started. An attempt was made for direct laryngoscopy – a grade 3b view was obtained and a size four microlaryngeal tube was passed successfully. 100% O₂, two doses of 1mg adrenaline IV, and 3mg atropine IV were given and the heart rate improved. Pulses were present and the defibrillator showed sinus rhythm; CPR was stopped and tracheostomy was continued. Due to abundant peri-tracheal fat, a number of tracheostomy tubes were tried before a secure tracheostomy was placed. However the microlaryngeal tube maintained airway patency.

An arterial line and larger cannula was secured. Propofol infusion and fentanyl IV were given to maintain anaesthesia and the patient was transferred to ICU.

On ICU, there was further difficulty in ventilation, with high airway pressures and saturations falling to the low 90s despite 100% O₂. It was thought the tracheostomy tube was abutting the carina or posterior tracheal walls. The ENT surgeons were called urgently and in the interim the patient was re-intubated with a size 7 ETT to maintain the airway. The ENT team changed the size 8 cuffed non-fenestrated tracheostomy tube for a size 7 Shiley with a proximal extension. Despite the change, ventilation remained difficult. An urgent chest X-ray was performed which showed a right-sided pneumothorax. A chest drain was inserted and a ‘hiss’ was noted on insertion, indicating a possible tension pneumothorax. Ventilation then improved.

Further history was taken from previous notes and discharge letters. It was noted that the patient had allergies to shellfish, penicillin, erythromycin, and diclofenac, but no history of exposure. She had a background of hypertension, angina, chronic kidney disease and previous breast cancer. She was taking Lisinopril, Diltiazem, Nicorandil, Tamoxifen, Sertraline and Omeprazole. Her tongue swelling improved markedly over the next two days with antibiotic treatment and regular dexamethasone. She was awakened once appropriate and haemodynamically stable. A nasendoscopy was performed by the ENT team on day six and nothing remarkable was noted, with swelling having regressed totally. She was decannulated on day eight and transferred to the ward. Lisinopril was stopped.

Discussion

This case demonstrated a severe, acute presentation of tongue swelling (glossitis) leading to upper airway obstruction. Although a number of conditions may cause glossitis: infection, trauma, anaemia, liver disease, malnutrition. Acute glossitis is a hallmark of angio-oedema. This is a rare, but life threatening condition that requires prompt recognition and treatment.

Angio-oedema may result from anaphylactic, hereditary, acquired or idiopathic processes. Some 12-24% of anaphylaxis cases present with angio-oedema.^{1, 2} Hereditary and acquired cases usually result from a deficiency of C1 esterase inhibitor deficiency, which causes an accumulation of bradykinin, leading to soft tissue oedema. Such an increase in bradykinin may be caused by angiotensin converting enzyme inhibitors, leading to angio-oedema.³ If no cause can be found, it is termed idiopathic.

Management of angio-oedema requires rapid airway assessment and management; resuscitation; and treatment of the underlying cause. Anaphylaxis should respond to standard management as outlined by the AAGBI.⁴ Angio-oedema from other causes requires cessation of the suspected causative agent³, and in an emergency, nebulized adrenaline to reduce airway swelling. Infusion of plasma derived or recombinant C1 Esterase Inhibitor may also rapidly improve symptoms.¹

Although airway support is the cornerstone of anaesthetic management, an acute, rapidly progressing case such as this requires a multi-disciplinary approach.⁵ Anaesthetists will require help from operating department practitioners and nurses to manage the initial airway compromise. A compromised airway presents a significant hazard to any form of anaesthesia, especially if it results in cardio-respiratory depression, which will expedite hypoxemia and impair tissue oxygenation. An awake, spontaneously ventilating approach to secure the airway needs to be undertaken. ENT staff should be scrubbed and ready to perform an emergency surgical tracheostomy if complete airway obstruction occurs or airway access cannot be secured.

An awake fibre-optic intubation can be attempted but this requires an experienced anaesthetist, timely access to equipment, preparation and a co-operative patient. These are unlikely to be provided in the resuscitation room. Fibre-optic manipulation causing bleeding or further swelling can lead to complete airway obstruction.

An inhalational induction to maintain spontaneous ventilation and then followed by direct laryngoscopy or fibre-optic intubation is another option and reduces the required co-operation of the patient. But this may cause haemodynamic instability in an already compromised patient and can lead to complete airway collapse.

An elective awake tracheostomy under local anaesthetic is the most likely route to ensure airway access without haemodynamic compromise.⁶ This will require a co-operative patient, senior help from trained operating department staff, and the ENT surgeons scrubbed and ready to perform a surgical tracheostomy if a percutaneous approach fails.

The Intensive Care Unit should be aware of the patient and ICU teams will be required to help with airway access as well as manage haemodynamic instability, secure arterial and central venous access. The patient will need further airway support and treatment in the Intensive Care Unit.

An acute upper airway obstruction therefore requires an emergent, yet controlled, approach to secure airway access and maintain oxygenation. Staff should have clear roles, ideally decided beforehand and practiced, with experience in the use of the equipment available. Senior ENT help should be available readily and again be versed in securing an emergency awake tracheostomy should other means fail or are not suitable.

As with any critical incident a debriefing should be undertaken to highlight points in the management of such patients that were handled well and those that were not, so that existing management plans can be improved and skills honed to improve management of future incidents.

Global Health can be defined as “an area for study, research, and practice that places a priority on improving health and achieving health equity for all people worldwide”. ¹ Article 25 of the 1948 Universal Declaration of Human Rights declares that, “everyone has the right to a standard of living adequate for the health of himself and of his family”. ² Unfortunately, the health disparity between high-income and low-income countries, as well as between individuals within a country, often makes this impossible, leaving many people living in unhealthy settings without sufficient access to care.  

The field of global health is concerned with the health of populations worldwide, focusing on issues that typically have global, political, and economic significance. These health issues usually transcend national boundaries and are best solved through international collaboration. ³ Global health initiatives aim to improve the health and wellbeing of impoverished, vulnerable, and underserved people worldwide. ¹ These initiatives include poverty reduction strategies, disease prevention measures (for HIV/AIDS, malaria, and tuberculosis, for instance), efforts to improve nutrition and food security, policy to raise environmental standards and living conditions, and the promotion of gender equality.  

In 2001, the Commission of the World Health Organization (WHO) recommended to fund global health with 0.1% of GDP. ⁴

The average expenditure per capita for health in low-income countries is estimated at $ 20 per year while that of Western countries is estimated at $ 947. The target to be reached to help out the most disadvantaged countries is $ 44-60 per capita, which would ensure the populations of the poorest countries with the access to essential health services. Directing the 0.1% of the GDP of developed Western countries to the aids for global health would mean closing the gap to reach the target base of $ 44-60 that would allow the saving of 8 million lives a year. ⁴

Despite the good intentions, there is still a marked disparity between the current spending levels and the commitments made by developed countries in a context in which, among other things, the percentage of aid for global health has been in decline for almost all donor countries.

Activists claim that only 10 per cent of global health research is devoted to conditions that account for 90 per cent of the global disease burden – the so-called ‘10/90 Gap’. ⁵ They argue that virtually all diseases prevalent in low income countries are ‘neglected’ and that the pharmaceutical industry has invested almost nothing in research and development for these diseases.

In fact, the WHO acknowledges that there are only three diseases that are genuinely ‘neglected’: African trypanosomiasis, leishmaniosis and Chagas disease. ⁶

A large proportion of illnesses in low-income countries are entirely avoidable or treatable with existing medicines or interventions. Most of the disease burden in low-income countries finds its roots in the consequences of poverty, such as poor nutrition, indoor air pollution and lack of access to proper sanitation and health education. The WHO estimates that diseases associated with poverty account for 45 per cent of the disease burden in the poorest countries. ⁷ However, nearly all of these deaths are either treatable with existing medicines or preventable in the first place.

If treatments exist for the majority of poor countries’ health problems, why then do mortality rates remain so high? Any discussion of this question must address the problem of access to essential medicines, which remains an intractable political and economic problem. According to the WHO, an estimated 30 per cent of the world population lacks regular access to existing drugs, with this figure rising to over 50 per cent in the poorest parts of Africa and Asia. ⁸ And even if drugs are available, weak drug regulation may mean that they are substandard or counterfeit.

Within these populations, it is the poorest socioeconomic groups that disproportionately suffer from a lack of access to existing medicines. ⁹ The implications of this failure of public health policy on global mortality are profound – according to one study, over 10 million children die unnecessarily each year, almost all in low-income or poor areas of middle income countries, mostly from a short list of preventable diseases such as diarrhoea, measles, malaria and causes related to malnutrition. ¹⁰

Many governments fail their populations in this respect by imposing punitive tariffs and taxes on medicines, and by skewing their spending priorities in favour of defence over health. The governments of poor countries hinder the creation of wealth, imposing obstacles in the way of owning and transferring property, imposing unnecessary regulatory barriers on entrepreneurs and businesses, and restricting trade through extortionate tariffs. It is these and other political failures that have left poor populations without the necessary resources to access the medicines that could so easily transform their quality of life.

In conclusion, it appears more and more urgent and necessary to decide where to direct our efforts and investment in research, without prejudice, analyzing all the possible strategies for tackling global health issues, including those standing beyond the current economic paradigm based on the market.

Resource allocation in medicine applies to two complementary levels of care. One pertains to the organisation of public health and the provision of general rules informing the management of the system (macro-allocation). On the other hand, there is the need to specify decision criteria for the daily practice of health care providers who have to decide on the utilisation of their allocated resources, while dealing with a demand that often exceeds supply (micro-allocation).¹

Beneficence, i.e. acting for the good of the patient, is one of the founding value of traditional ethics in medicine. However, the picture has changed when the core value of medicine shifted toward the centrality of the human person and the ideal of self-determination. The patient is now a 'health care user' who consults a professional whose knowledge and expertise is used in order to arrive at options. Good medical practice seems the result of a 'contract bargaining', which must take into account different criteria: clinical indication, patient preferences and subjective values, and appropriateness within the social context. Controlling how these three elements interact with each other requires a constant commitment and synchronised interventions.²

For cultural reasons, physicians consider, quite rightly, the costs of their interventions to be incommensurable with the life and the restoration to health of the diseased person. The most difficult problem in the distribution of resources remains the finding of convincing criteria to provide guidance, when often painful choices have to be made in the face of inadequacies in the availability of resources.³

Intensive care is one of the most expensive specialities of medicine and intensive care beds nowadays represent a limited resource.^{4, 5}  The lack of beds is a daily problem in many ICU^{6, 7} and bed allocation has been considered one of the thorniest and stressful aspects of the intensivist's job.⁸  Studies have shown that resource use is often inefficient in European ICU. One of the main reasons for this inefficiency has been identified as nursing force “waste”.⁹ 

Monitoring and support of deficient vital functions are the main aims of intensive care. Usually, intensivists carry out the adequate diagnostic procedures and necessary medical and surgical treatments required to improve patient outcomes. There has been a considerable international effort to define the ethical,  clinical and economical criteria for admission to ICU and to draft the relevant guidelines. The fundamental point is that resources should be utilised appropriately, i.e. that the patient be of the right category, in the right place and at the right time. Furthermore, ethics dictates that resources be allocated where they are more likely to make an impact.^10-13

ICU admission and discharge can be ruled by means of a priority scale which classifies patients based on the expected benefit to result from intensive treatment.¹⁴ However, while it may be relatively easy to create “on-paper” scenarios affirming that patients who are too critical or not critical enough to benefit should not be admitted to intensive care, identifying these patients in everyday practice is far from simple.

As far as a reasonable doubt may be considered regarding the irreversibility of the clinical status, it is appropriate to initiate or continue intensive treatment. On the contrary, if the irreversibility of the clinical setting is deemed to be reasonably certain, it is appropriate not to initiate or to withdraw intensive measures to spare the patient the undue prolongation of the dying process. Excessive treatment is ethically unfair and should be strongly condemned, because it determines an inappropriate use of the means of treatment; it is likely to cause harm and pain to the patient and fails to respect the patient's dignity in death. Excessive treatment also increases the suffering of family members, is frustrating for care providers and generates an inequitable distribution of resources by curtailing them for other patients. The withdrawal of an intensive treatment, which was previously initiated because deemed to be indicated and accepted, or because the patient's clinical status and relevant prognosis were not clear enough at the time, should be considered whenever the clinical picture counter-indicates treatment continuation, the patient withdraws consent, or a previously defined therapeutic limit is reached.¹⁵ 

Immortality has always been an ambition for human beings. Today's medicine appears to be instrumental in dealing with this type of issues by making promises that will be hard not to break. The most urgent form of action to be undertaken regards these unwarranted expectations that society holds about the efficacy of medicine. The message to put across ought to be that death is inescapable and that the most severe diseases are incurable.

Once the inevitability of resorting to often dramatic measures in today's health care system is postulated, we are confronted with the problem of finding an ethical justification to subsequent decisions. On the basis of the choices made necessary by the paucity of available resources, medical treatment would be “apportioned”, i.e., distributed according to commitments and rules, with the inevitable exclusion of some from the utilization of the services themselves.

Rationalisation, intended as best utilisation and fair limitation, is an economic necessity, juridically and ethically legitimate. The ultimate objective must remain that of equitable apportionment. 

Introduction

Major Obstetric haemorrhage (MOH) remains one of the leading causes of maternal mortality & morbidity worldwide. In the 2003-2005 report of the UK Confidential Enquiries into Maternal Deaths, haemorrhage was the third highest direct cause of maternal death (6.6 deaths/million maternities) with the rate similar to the previous triennium ^{1, 2}. Postpartum haemorrhage (PPH) accounts for the majority of these deaths. This triennium, 2006-2008, unlike in previous reports there has been a change in the rankings of direct deaths by cause. Deaths from haemorrhage have dropped, to sixth place, following genital tract sepsis, preeclampsia, thromboembolism, amniotic fluid embolism and early pregnancy deaths ³. A well-defined multidisciplinary approach that aims to act quickly has probably been the key to successful management of MOH. In the developing world, several countries have maternal mortality rates in excess of 1000 women per 100,000 live births, and WHO statistics suggests that 25 % of maternal deaths are due to PPH, accounting for more than 100,000 maternal deaths per year ⁴.The blood loss may be notoriously difficult to assess in obstetric bleeds ^{5, 6}. Bleeding may sometimes be concealed & presence of amniotic fluid makes accurate estimation challenging.

Definition

MOH is variably defined as blood loss from uterus or genital tract >1500 mls or a decrease in haemoglobin of >4 gm/dl or acute loss requiring transfusion of >4 units of blood. Blood loss may be:

1. Antepartum: Haemorrhage after 24th week gestation & before delivery; for example: placenta praevia, placental abruption, bleeding from vaginal or cervical lesions.

2. Postpartum: Haemorrhage after delivery

• Primary PPH: Within 24 hours of delivery, which is >500 mls following vaginal delivery & > 1000mls following a caesarean section ⁷.
• Secondary PPH: 24 hours to 6 weeks post-delivery; for example: Uterine atony, retained products of conception, genital tract trauma, uterine inversion, puerperal sepsis, uterine pathology such as fibroids ⁸.

PPH can be minor (500-1000 mls) or major (> 1000 mls). Major PPH could be divided to moderate (1000-2000 mls) or severe (>2000 mls).

Causes

Causes of PPH may be conveniently remembered using 4 T’s as a mnemonic:

• Tone(Uterine atony)
• Tissue (retained products)
• Trauma( cervical & genital tract trauma during delivery)
• Thrombosis (coagulation disorder)

Other Risk factors include:-Prolonged labour, multiple pregnancy, polyhydramnios, large baby, obesity, previous uterine atony & coagulopathy.

Prevention

The most significant intervention shown to reduce the incidence of PPH is the active management of the third stage of labour (see below).Other measures to prevent or reduce the impact of MOH include

• Avoidance of prolonged labour
• Minimal trauma during assisted vaginal delivery
• Detection & treatment of anaemia during pregnancy
• Identification of placenta praevia by antenatal ultrasound examination.
• Where facilities exist, magnetic resonance imaging (MRI) may be a useful tool and assist in determining whether the placenta is accreta or percreta. Women with placenta accreta/percreta are at very high risk of major PPH. If placenta accreta or percreta is diagnosed antenatally, there should be consultant-led multidisciplinary planning for delivery ⁹.

Active management of the third stage

This represents a group of interventions including early clamping of the umbilical cord, controlled cord traction for placental delivery & prophylactic administration of uterotonic at delivery (e.g. oxytocin) ¹⁰. Active management of the third stage is associated with a lower incidence of PPH and need for blood transfusion ¹¹. A longer acting oxytocin derivative, carbetocin, is licensed in the UK specifically for the indication of prevention of PPH in context of caesarean delivery. Randomised trials suggest that a single dose (100 mcg) of carbetocin is at least as effective as oxytocin by infusion ^{12, 13}.

Management of MOH

Pregnant women are often young, healthy & have an increased blood volume of up to 20 % at term and therefore likely to compensate well to haemorrhage until the circulating blood volume is very low ¹⁴. MEOWS are a useful bedside tool for predicting morbidity. A validation study of the CEMACH recommended modified early obstetric warning system (MEOWS) in all obstetric inpatients to track maternal physiological parameters, and to aid early recognition and treatment of the acutely unwell parturient.  In addition, blood loss may sometimes be concealed and difficult to calculate. More commonly massive haemorrhage may be obvious; signs other than revealed haemorrhage include:

• Tachycardia
• Hypotension( BP may not drop until significant blood is lost)
• Pallor
• Oliguria
• Cool peripheries
• Lower abdominal pain

Management of anticipated MOH

On some occasions, cases at high risk of MOH can be predicted; e.g. caesarean section in a lady with a low lying placenta and previous uterine scar. These cases may be at a risk of placenta accreta and massive blood loss.

• 2 large bore IV cannulae
• Rapid infusion device or pressure bags in theatre
• Blood warmer & warming blanket
• Blood cross-matched & available
• Consider preoperative invasive monitoring
• Consider cell salvage if available (see below)
• Consider interventional radiological procedures if available ( see below)

Management of unanticipated MOH

Management involves four components, all of which must be undertaken SIMULTANEOUSLY: communication, resuscitation, monitoring and investigation, arresting the bleeding ^{9, 15}. Most maternity units in UK have CODE RED bleep system for alerting MOH.

Communication & teamwork:

Communication and teamwork are essential in cases of both anticipated & unanticipated maternal haemorrhage. This includes:

• Call for help. Alert the midwife-in-charge, senior obstetrician & anaesthetist.
• Alert Blood transfusion service & haematologist.
• Alert portering service for transport of blood samples & collection of blood products
• Check blood is available. In the UK 2-4 units of O-neg blood is kept on labour ward for emergency use.
• Allocate roles to team members.
• Ensure departmental guidelines exist for the management of MOH & regularly practice ‘fire drills’.
• Alert one member of the team to record events, fluids, drugs and vital signs ⁹.
• The use of standard form of words (such as ‘on going major obstetric haemorrhage’, ‘we need compatible blood now or group specific blood’) ⁹.

Goals of management:

• Early identification of maternal bleed and institution of major haemorrhage drill
• Rapid access to infusion of fluid in first instance with rapid availability & administration of blood.
• Avoidance/limitation of complications of massive blood transfusion namely: acid/base disturbance, transfusion related acute lung injury (TRALI), hypocalcaemia, hyperkalaemia, hypothermia & thrombocytopenia.
• Efficient team working & management decision making.

Resuscitation & immediate management:

• ABC, 100% oxygen
• 2 large bore cannulae & bloods for X-match
• Fluid resuscitation; crystalloid/colloid 2000mls via rapid infuser or pressure bags e.g. Level 1 Rapid infuser ( can achieve >500mls/min warmed fluid flow)
• Fluid therapy and blood product transfusion ⁹
• Crystalloid Up to 2 litres Hartmann’s solution
• Colloid up to 1–2 litres colloid until blood arrives
• Blood Crossmatched
• If crossmatched blood is still unavailable, give uncrossmatched group-specific blood OR give ‘O RhD negative’ blood
• Fresh frozen plasma 4 units for every 6 units of red cells or prothrombin time/activated partial thromboplastin time > 1.5 x normal (12–15 ml/kg or total 1litres)
• Platelets concentrates if platelet count < 50 x 10⁹
• Cryoprecipitate If fibrinogen < 1 g/l
• Thromboelastography and rotational thromboelastometry coagulation tests: In most cases, medical and transfusion therapy is not based on the actual coagulation state because conventional laboratory test results are usually not available for 45 to 60 minutes. Thromboelastography and rotational thromboelastometry are point-of-care coagulation tests. A good correlation has been shown between thromboelastometric and conventional coagulation tests, and the use of these in massive bleeding in non-obstetric patients is widely practiced and it has been proven to be cost-effective.
• A 2006 guideline from the British Committee for Standards in Haematology ^{1, 4}summarizes the main therapeutic goals of management of massive blood loss is to maintain:
  • Haemoglobin > 8g/dl
  • Platelet count > 75 x 10⁹/l
  • Prothrombin < 1.5 x mean control
  • activated prothrombin times < 1.5 x mean control
  • Fibrinogen > 1.0 g/l.
• In addition, the Confidential Enquiry into Maternal and Child Health recommends that women with known risk factors for PPH should not be delivered in a hospital without a blood bank on site ¹.
• Transfer to theatre.
• Non-surgical intervention for uterine atony.
• Bimanual uterine compression (rubbing up the fundus) to stimulate contractions.
• Ensure bladder is empty (Foley catheter, leave in place). ‘Rub up ‘the uterus
• Syntocinon 5 units by slow intravenous injection (may have repeat dose).
• Ergometrine 0.5 mg by slow iv/im injection (contraindicated in women with hypertension) ¹⁶.
• Syntocinon infusion (40 units over 4 hours).
• Carboprost 0.25 mg by intramuscular injection repeated at intervals of not less than 15 minutes to a maximum of 8 doses (contraindicated in women with asthma).
• Direct intramyometrial injection of carboprost 0.5 mg im (Haemobate or Prostaglandin F2a) with responsibility of the administering clinician as it is not recommended for intramyometrial use. Can be repeated up to 5 doses (contraindicated in women with asthma, may cause bronchospasm, flushing & hypertension ¹⁷).
• Misoprostol 1000 micrograms rectally.
• If pharmacological measures fail to control the haemorrhage, initiate surgical haemostasis sooner than later.

Surgical treatment and other interventions

The most common cause of primary PPH is uterine atony. However, clinical examination must be undertaken to exclude other or additional causes:

• Retained products (placenta, membranes, clots)
• Vaginal/cervical lacerations or hematoma
• Ruptured uterus
• Broad ligament hematoma
• Extra genital bleeding (for example, subcapsular liver rupture)
• Uterine inversion.

Intrauterine balloon tamponade is an appropriate first line ‘surgical’ intervention for most women where uterine atony is the only or main cause of haemorrhage. If this fails to stop the bleeding, the following conservative surgical interventions may be attempted, depending on clinical circumstances and available expertise:                                                                               

• Balloon tamponade (Bakri/Rusch balloon, Foley’s/condom catheter, Sengstaken-Blakemore tube ^18-21
• Haemostatic brace suturing (such as B-Lynch or modified compression sutures).
• Bilateral ligation of uterine arteries.
• Bilateral ligation of internal iliac (hypogastric) arteries.
• Selective arterial embolisation or balloon occlusion radiologically.
• Compression/ clamping aorta to buy time.
• Uterine replacement if uterine inversion

It is recommended that a laminated diagram of the brace technique be kept in theatre. Resort to hysterectomy sooner rather than later (especially in cases of placenta accreta or uterine rupture). A second consultant clinician should be involved in the decision for hysterectomy.

Interventional Radiological techniques

Interventional techniques are gaining popularity if the facilities & expertise exist and are especially useful for the anticipated massive bleeds e.g. planned LSCS in a woman with anticipated placenta accrete. Though evidence of effectiveness is still limited, there are increasing case reports of its successful use. This suggests that prophylactic arterial catherisation (with a view to embolisation) could be considered where facilities permit until such time as further evidence becomes available ^22-28.

• Bilateral internal iliac artery balloons may be placed electively & inflated at C. section/ should bleed occur.
• Selective pelvic artery (internal iliac arteries, anterior division of internal iliac or uterine artery) embolisation can be performed.
• Complications appear rarely & include: haematoma, false aneurysms & lower limb ischemia.

Interventional radiology may be considered in cases of placenta praevia with accreta if intra-arterial balloons can be placed in the radiology department before the woman goes to theatre for caesarean section. Follow up studies of women who had undergone arterial embolisation for control of PPH suggest that the intervention does not impair subsequent menstruation and fertility ^{29, 30}.

Intraoperative cell salvage in obstetrics (ICSO)

Cell salvage has now been used in numerous cases of obstetric bleeds and appear safe. Concerns relate to re-infusion of foetal cells which could theoretically cause haemolytic disease in future pregnancies and also the potential for amniotic fluid embolus. If cell salvage techniques are utilised, separate suction of amniotic fluid is recommended and a leukocyte depletion filter used during re-infusion of salvaged blood. Setting up cell salvage measures should not divert staff an attention from initial resuscitation.

Intraoperative cell salvage (the process whereby bloodshed during an operation is collected, filtered and washed to produce autologous red blood cells for transfusion to the patient) is commonly being used in cardiac, orthopaedic and vascular surgery with relative reduction of blood transfusion by 39% and absolute risk reduction by 23%, with cell salvage not appearing to impact adversely on clinical outcomes ^{31, 32}. Although large prospective trials of cell salvage with auto transfusion in obstetrics are lacking, to date, no single serious complication leading to poor maternal outcome has been directly attributed to its use. Several bodies based on current evidence have endorsed cell salvage in obstetrics. Current evidence supports the use of cell salvage in obstetrics, which is likely to become increasingly commonplace, but more data are required concerning its clinical use ³³. A National UK survey in 2007 showed that, in 2005–2006, 38% of all UK maternity units were using cell salvage and that 28% incorporated cell salvage into their massive haemorrhage guidelines ³⁴. In particular, this survey showed that a lack of training was the main perceived barrier to its use: 48% of units specifically stated that their reason for not using cell salvage was lack of training and equipment, with fears about safety being expressed by only 10%. However, the potential difficulty is the effective removal of amniotic fluid and the degree of contamination with fetal red cells with potential maternal sensitization, intraoperative cell salvage may be a useful technique in women who refuse blood or blood products (Jehovah’s Witnesses guideline) ⁹ or those where massive blood loss is anticipated (placenta percreta or accreta). For women who are Rh-negative, to prevent sensitization, the standard dose of anti-D should be given and a Kleihauer test taken 1 hour after cell salvage has finished, to determine whether further anti-D is required ³⁵.

Recombinant activated factor VII (rFVIIa)

Recombinant activated factor VII (rFVIIa) was developed for the treatment of haemophilia. Over the past decade, it has also been used to control bleeding in other circumstances. A 2007 review identified case reports of 65 women treated with rFVIIa for PPH ³⁶.Although the case reports suggested that rFVIIa reduced bleeding, 30 of the 65 women underwent peripartum hysterectomy and particular caution is required in interpreting data from uncontrolled case reports. In the face of life-threatening PPH, and in consultation with a haematologist, rFVIIa may be used as an adjuvant to standard pharmacological and surgical treatments. A suggested dose is 90 micrograms/kg, which may be repeated in the absence of clinical response within 15–30 minutes ³⁷. Although there is no clear evidence of thrombosis with the use of rFVIIa in obstetric practice, there have been case reports of thrombosis with the use in cardiac surgery ^38-40. Women with PPH are particularly susceptible to defibrination (severe hypofibrinogenaemia) and this is particularly relevant to the most severe cases that will be considered for rFVIIa; rFVIIa will not work if there is no fibrinogen and effectiveness may also be suboptimal with severe thrombocytopenia (less than 20 x 10⁹/l).Therefore, fibrinogen should be above 1g/l and platelets greater than 20 x 10⁹/l before rFVIIa is given. If there is a suboptimal clinical response to rFVIIa, these should be checked and acted on (with cryoprecipitate, fibrinogen concentrate or platelet transfusion as appropriate) before a second dose is given ^36-40.

Anaesthetic management ¹⁵:

• GA with RSI is generally advocated if actively bleeding or coagulopathy.
• Reduce dose of induction agent if severe on going bleeding.
• Regional anaesthesia is relative contraindication but may be maintained if the patient has an epidural insitu & bleeding is controlled.
• Alert Blood bank & haematologist.
• Consider arterial line, central line and urinary catheter but only after definitive treatment has commenced. Their insertion must not delay resuscitation & fluid management.
• Use fluid warmer & aim to keep the patient normothermic.
• Regular monitoring of haemoglobin level and coagulation using near patient devices if available (e.g. Haemacue). FFP, platelets transfusion & cryoprecipitate may be necessary if coagulopathy develops. Liaise early with haematology department for optimal & timely product replacement.
• Perioperative monitoring as per AAGBI guidelines.
• Recording of parameters on a flow chart such as the modified obstetric early warning system charts.
• Consider systemic haemostatic agents such as Aprotonin, Vit K, Tranexemic acid, Recombinant factor VII a (Novo seven R). Although evidence is conflicting, there is a consensus view that fibrinolytic inhibitors seldom, if ever, have a place in the management of obstetric haemorrhage ^{41, 42}.
• Postoperative management includes transfer to ITU/HDU.
• Anticipate coagulopathy & treat clinically until coagulation results available.
• It is also important that, once the bleeding is arrested and any coagulopathy is corrected, thromboprophylaxis is administered, as there is a high risk of thrombosis. Alternatively, pneumatic compression devices can be used, if thromboprophylaxis is contraindicated in cases of thrombocytopenia.

Conclusion

Globally, postpartum haemorrhage (PPH) is the leading cause of maternal morbidity and mortality. Major obstetric haemorrhage is managed by multidisciplinary approach. In the current treatment of severe PPH, first-line therapy includes transfusion of packed cells and fresh-frozen plasma in addition to uterotonic medical management and surgical interventions. In persistent PPH, tranexamic acid, fibrinogen, and coagulation factors are often administered. Secondary coagulopathy due to PPH or its treatment is often underestimated and therefore remains untreated, potentially causing progression to even more severe PPH. The most postnatal haemorrhage is due to uterine atony and can be temporarily controlled with firm bimanual pressure while waiting for definitive treatment.

Background

Nerve blocks have a variety of applications in anaesthesia enabling an extra dimension for patients with regards to their pain control and anaesthetic plan.  Anaesthetists can perform nerve blocks by a range of methods including landmark techniques and ultrasound guidance, with both of these techniques having the potential to be used with a nerve stimulator.

Nerve blocks are associated with complications including nerve damage, bleeding, pneumothorax and failure.  Ultrasound, if used correctly, may help limit such complications.¹ NICE guidance on the use of ultrasound guidance for procedures, has evolved over the years.  Ultrasound guidance is now considered an essential requirement for the placement of central venous lines² and is recommended when performing nerve blocks.³

Method

This survey aimed to assess the methods used by anaesthetists in performing nerve blocks and audited the use and competencies of clinicians in performing such blocks under ultrasound guidance and landmark techniques. This survey also looked at whether performing nerve blocks under ultrasound guidance was hindered by the lack of availability of appropriate resolution ultrasound machines in the workplace.

A paper survey was completed by anaesthetists of all grades at Kettering general hospital, UK and Birmingham Heartlands Hospital, UK between October and December 2011.  The survey consisted of a simple, easy to use, tick box table and a generic area in which participants made further contributions.  From this we ascertained the following:

• Grade of clinician.
• Any courses undertaken in ultrasound guided nerve blocks.
• Which nerve blocks the clinicians felt they could perform competently with either method (landmark versus ultrasound guided).
• In the event the anaesthetist could perform a block with or without ultrasound guidance; which method was used if ultrasound equipment was available.
• Was the ability to perform ultrasound guided nerve blocks limited by the availability of an ultrasound machine.

The term “landmark technique” is used when the landmark technique is combined with or without a nerve stimulator and the term “ultrasound technique” when ultrasound guidance is used with or without a nerve stimulator.

Results

We surveyed a total of 52 anaesthetists, subdivided into Consultants 26 (50%), ST/staff grade 17 (33%), CT trainees 9 (17%).  Of all grades, only 50% had completed a course in ultrasound guided nerve blocks.  42% of clinicians had encountered situations when they could not use ultrasound guidance for a nerve block because there was no ultrasound machine available at the time of the procedure. 

The competencies of clinicians with the landmark and ultrasound technique varied depending on the type of nerve block and the grade of clinician (figure 1). 

Various routinely performed blocks were surveyed and this revealed a good comparison of the use of ultrasound and landmark technique.  For the Interscalene block, the consultants and middle grades combined were competent in performing this block, with the landmark technique 56% and the ultrasound technique 33%.  For the Lumbar plexus block, 0% of the consultants surveyed felt competent in performing this block with the ultrasound technique compared to 73% with the landmark technique. The majority of clinicians felt competent in performing the TAP block with the ultrasound technique, 65% versus 35%, for the landmark technique.

Figure 1. This table illustrates competencies for different nerve blocks with the landmark technique and ultrasound technique for different grades of anaesthetists.

Discussion

The findings of this survey and audit have a range of implications for anaesthetists in the workplace: 

1) Junior grades of doctors do not feel competent in performing nerve blocks.  This may lead to a reliance on senior doctors during on calls to assist in performing blocks such as femoral and TAP blocks.  Specific training geared towards junior doctors to make them proficient in such blocks would enable them to provide an anaesthetic plan with more autonomy.

2) A large percentage of consultant grade clinicians felt competent in performing nerve blocks with the landmark technique but not in performing the same blocks with ultrasound guidance.  This has implications for training because consultants are the training leads for junior grades of anaesthetists.  If consultants do not feel competent in the use of ultrasound guidance for nerve blocks, this could lead to a self perpetuating cycle.

3) Only 50% of clinicians in this survey had completed a course for ultrasound guided nerve blocks, this coupled with the finding that clinicians did not feel comfortable in performing nerve blocks with ultrasound, indicates the possible need for local training accessible to clinicians to improve their everyday practice.

4) It has been shown that ultrasonic guidance improves the success rate of interscalene blocks.⁴  The practice amongst clinicians in this survey reveals that the majority of anaesthetists (middle and consultant grades) are competent with the landmark technique 56% compared to the ultrasound technique 36%.  This also highlights a training deficit which if addressed would enable clinicians to offer a more successful method of performing the interscalene block.

5) This survey highlighted the lack of availability of appropriate ultrasound machines in different departments, leading to some clinicians utilising the landmark technique, when ultrasound guidance was the preference.  This has the potential of a patient receiving a nerve block technique which may have been riskier and less efficient.  This highlights a potential need for investment and accessibility of appropriate resolution ultrasound machines in the different work places of a hospital environment.

The main limitation of this project was the small number of clinicians in the respective hospitals the survey was performed in.  However, we feel the results reflect the practice of clinicians across most anaesthetic departments.  The recommendations highlight a training need for anaesthetic trainees in the use of ultrasound guided nerve blocks.   This survey could form the basis of a much larger survey of clinicians across the UK to provide a more insightful review of the competencies and preferences of anaesthetic trainees in performing nerve blocks and the availability of appropriate resolution ultrasound machines.

The difference in the number of clinicians in each category limited comparisons between groups.  A larger cohort of participants would enable comparison of nerve block techniques between different grades of clinicians.

This survey included all clinicians regardless of their sub-specialist interest.  This may result in a skewing of results, depending on the area of interest of the clinicians surveyed.

This work only highlights the competencies and preferences of clinicians in performing nerve blocks.  No extrapolation can be made to complications that arise from the choice of either technique.  Studies have shown an improved success rate when performing nerve blocks with ultrasound.⁴ However this does not directly apply to a specific clinician who may have substantial experience in their method of choice in performing a nerve block.

Case report

A 78 year old man was admitted for re-fashioning of a prolapsing colostomy. Nine months previously he had undergone a juxtarenal aortic aneurysm repair complicated by ischaemic colitis, for which he had a sigmoid colectomy and a further laparotomy for refashioning of the stoma.

His past medical history consisted of anaemia, stable angina, superficial bladder cancer, Stage 4 chronic kidney disease, type 2 diabetes mellitus and osteoarthritis. He weighed 77 kg and his exercise tolerance was 100 yards, with the aid of a stick. His medications included doxazosin, quinine sulphate, perindopril, simvastatin, ferrous sulphate, isosorbide mononitrate and aspirin.

On examination, he was apyrexial with a blood pressure of 170/70 mm Hg, a heart rate of 65 bpm, a respiratory rate of 14 bpm and Sa0₂ of 98% on room air. Serum laboratory tests showed a prothrombin time of 13.4 sec (normal range 9.0 – 13.0 sec), haemoglobin 10.2 g/dL (13.0 – 16.7 g/dl), platelets 131 x10⁹/L (150 – 400 x10⁹/L), sodium 139 mmol/L, potassium 4.2 mmol/L, urea 15.7 mmol/L (2.5 – 7.0 mmol/L), creatinine 196 umol/L (50 – 130 umol/L) and eGFR 29 ml/min/1.73m² (>60ml/min/1.73m²).

His preoperative pulmonary function tests showed an FVC of 2.78L (93.8% predicted), a reduced FEV1 of 1.66L (75.2% predicted) and FEV/FVC of 59.87%. His ECG showed normal sinus rhythm. A CPEX test taken 12 months previously showed moderately reduced peak aerobic capacity, with a peak V0₂ of 11 ml/kg/min and an anaerobic threshold (AT) of 7 ml/kg/min.

In the anaesthetic room, the patient was connected to standard monitoring in accordance with AAGBI Guidelines and venous access secured with an 18 g biovalve cannula. Following pre-oxygenation, anaesthesia was induced using fentanyl 200 mcg, midazolam 2 mg, propofol 120 mg and atracurium 50 mg. Tracheal-intubation was achieved (grade 1 view) using an 8.0 mm cuffed endotracheal tube (lo-contour). A TAP block was administered following induction using ultrasound guidance (Sonosite ‘micromax’). A 50 mm insulated Stimi-Plex needle was used to inject a total of 40 ml levobupivacaine 0.375% bilaterally. Anaesthesia was maintained using a mixture of air, oxygen and sevoflurane (1.3 – 2.3 ETAA range). Intravenous (IV) paracetamol 1 g was given intraoperatively. The prolapsing colon was dissected through a circumstomal incision. A 10 cm length of colon was resected after ligation and division of the mesenteric vessels. The new end colostomy was fashioned with interrupted mucocutaneous sutures. Blood loss was minimal and there were no intraoperative complications. The duration of surgery was 1.5 hrs.

The patient spent 30 minutes in the postoperative recovery unit. He was awake, orientated and pain free throughout this period and clinical observations were stable. The patient remained pain-free on the ward and did not require any postoperative opioids. He was medically fit for discharge the following day.

Discussion

There are no previous case reports to our knowledge describing the use of TAP blocks in a patient with such poor CPEX testing preoperatively (AT = 7 ml/kg/min). CPEX testing has been shown to be an independent predictor of morbidity, mortality and length of hospital stay after major abdominal surgery.¹ The anaerobic threshold marks the onset of anaerobic metabolism as a result of inadequate oxygen delivery. It is not affected by patient effort and therefore provides a reliable patient specific measurement of functional capacity.² An AT of at least 11 ml/kg/min is recommended to safely undertake major surgery.² A combination of an AT of <11 ml/kg/min with ECG evidence of myocardial ischaemia is associated with high mortality and poor outcome. ³One study showed a mortality of 42% in those with ischaemic heart disease (IHD) and an AT <11 ml/kg/min, compared with just 4% in those with no IHD.⁴

Postoperative morbidity and mortality most often occurs in patients with pre-existing cardiorespiratory disease and a reduced functional capacity, due to their inability to withstand the additional physiological demands placed upon them by major surgery. Many of these patients develop features of organ hypoperfusion due to poor cardiorespiratory reserve.⁵

Our patient had an AT of 7 ml/kg/min and poor respiratory reserve (exercise tolerance of 100 yards, FEV/FVC 59.87% of predicted) but underwent uneventful intra-abdominal surgery with a good recovery and short length of hospital stay. Contributing factors may have been the anaesthetic technique used, as well as the surgical approach via a parastomal incision. Good intraoperative and postoperative control of cardiovascular parameters, temperature and pain are well known to reduce the surgical stress response and postoperative morbidity, and to improve postoperative outcome.⁶ Our patient was cardiovascularly stable throughout the perioperative period. His pain was well controlled with no opioid requirements due to the use of bilateral TAP blocks, and this probably contributed to his uneventful recovery, with no critical care requirement.

CPEX testing is not universally accepted as a useful preoperative assessment tool. In studies assessing it as a reliable predictor of outcome, there is heterogeneity in the degree of clinician blinding used. Blinding was used in some studies,¹ whilst in other instances, clinicians were aware of the CPEX results and changed their management accordingly. This obscures the true relationship between patient outcome and CPEX-derived measures of risk.⁷

TAP blocks were first described in 2001⁸ and have been shown to significantly reduce postoperative morphine consumption following abdominal surgery by up to 70%. They reduce pain scores at rest and during mobilisation in the early postoperative period (0-6 hours), and in the first 24 hours.⁹ The reduced requirement for morphine also leads to a reduction in postoperative nausea, vomiting and sedation.⁹ It may be possible that the ultrasound guided TAP block confers advantages in procedures with moderate surgical trauma to minimize pain and reduce opioid usage, thereby promoting faster recovery and discharge.⁸ TAP blocks were the chosen method of analgesia in our patient as they would elicit the least physiological disturbance, but would provide good postoperative analgesia, without opioid-related side effects. This was particularly beneficial, as his pre-existing renal impairment put him at increased risk of opiate toxicity. TAP blocks eliminate somatic pain relating to the surgical incision but do not treat visceral pain. However, our patient tolerated a 10 cm bowel resection with bilateral TAP blocks and intravenous paracetamol. A similar effect has been observed in other studies but the mechanisms behind it are unclear. One theory is that there is an analgesic effect due to high systemic levels of local anaesthetic.¹⁰

The use of CPEX testing to determine fitness for surgery should be interpreted with caution as newer anaesthetic and surgical techniques develop. Our patient had IHD and an AT which showed a significantly increased level of risk. However, a combination of regional anaesthesia and a cardio stable general anaesthetic with minimally invasive surgery, allowed a rapid and uneventful recovery with no opioid requirements and a short length of hospital stay.

Acute Lung Injury (ALI) is a continuum of clinical and radiographic changes affecting the lungs, characterised by acute onset severe hypoxaemia, not related to left atrial hypertension, occurring at any age.  At the severe end of this spectrum lies Acute Respiratory Distress Syndrome (ARDS) and therefore unless specifically mentioned this review will address ARDS within the syndrome of ALI. 

It was first described by Ashbaugh in the Lancet in 1967. This landmark paper described a group of 12 patients with “Respiratory Distress Syndrome” who had refractory hypoxaemia, decreased lung compliance, diffuse infiltrates on chest radiography and required positive end expiratory pressure (PEEP) for ventilation.¹

• Non-specific radiological findings which are subject to inter-observer variability
• Oxygenation criteria is independent of  inspired oxygen concentration or ventilator settings including lung volumes and PEEP
• Excluding cardiac causes of pulmonary oedema including left ventricular failure, mitral regurgitation and cardiogenic shock, in the ICU setting is difficult even when pulmonary artery catheters are used
• The definition includes a heterogeneous population who behave very differently in response to treatment, duration of mechanical ventilation and severity of pulmonary dysfunction.

• Bilateral patchy consolidation, which may or may not be symmetrical
• Normal vascular pedical width
• Air bronchograms
• Pleural effusion may be present
• 10-15% patients have pneumothoraces independent of ventilator settings

Computer tomography of the chest can show the heterogeneous nature of ALI, with dependent areas of the lung showing patchy consolidation with air bronchograms, atelectasis and fibrosis.  As with plain radiography there may be pneumothoraces present.

Computer tomography and Chest radiograph of ARDS

• Barotrauma – alveolar overdistension associated with ventilation at high volumes
• Volutrauma – alveolar overdistension associated with ventilator high pressures
• Biotrauma – repeated opening and closing of collapsed alveoli causing shearing stress which can initiate a proinflammatory process

Introduction

• High arched palate.
• Protruding maximally incisor (Buck teeth)
• Wide & short Neck

Discussion

Introduction

Day-case surgery is of great value to patients and the health service. It has rapidly expanded as a cost-effective and resource-conserving surgical intervention. However, the ability to deliver a safe and cost-effective general anesthetic with minimal side effects and rapid recovery is demanded in a day-case surgery unit. Pain and emesis are the two major complaints after day case surgery. Opioids are the agents of choice for severe pain. However, this class of analgesics is associated with dose-dependent adverse effects such as PONV, sedation, respiratory depression, resulting in delayed discharge or prolonged hospital stay. Non-opioid analgesics, e.g. acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), are often used alone or as adjuncts to opioids because of fewer adverse effects compared to opioids alone. However, NSAIDs also have side effects [1]. Lornoxicam is a new NSAID that belongs chemically to oxicams, a chemical class including piroxicam and tenoxicam. Lornoxicam is a potent inhibitor of cyclo-oxygenase and the only oxicam with a 15 times shorter half-life than piroxicam and tenoxicam [2]. In addition, lornoxicam can be given by I.V. route. Lornoxicam has a better safety profile than diclofinac and naproxen with regards to renal and hepatic function tests. In addition to better GIT tolerability compared to selective COX2 inhibitors; it is completely metabolized to inactive metabolites [2,3]. Lornoxicam has been successfully used in prevention and treatment of postoperative pain. However, evaluation of the perioperative analgesic efficacy of lornoxicam in day-case surgery has not yet been studied. This randomized, double blinded study was designed to compare the quality of perioperative analgesia as well as side effects of IV lornoxicam versus fentanyl in patients scheduled for minor to moderate day-case ENT surgical procedures. Materials and Methods: Male or female patients (aged 18-60 yr) were eligible for inclusion in the study. After obtaining the approval of the Hospital Research & Ethical Committee and patient’s informed consent, patients were randomized into three groups of ASA class I and II, scheduled to undergo minor to moderate day-case ENT surgical procedures e.g. tonsillectomy, excision of ENT lesion (e.g. vocal cord nodules and cysts), polypectomy and endoscopic sinus operations were enrolled in this randomized, double blinded study between May and December 2008. Exclusion criteria were patients with body mass index (BMI) > 30%, drug or alcohol abuse, and known allergy to NSAIDs, paracetamol or any contraindications for opioid use.  The protocol was similar for all patients. Prior to surgery, patients were educated in the use of the 10 – point visual analog scale (VAS) for pain assessment (0 = no pain to 10 = maximum pain). No premedication was given. In the holding area, an IV cannula was inserted and an IV infusion of Lactated Ringer’s was started. HR, MAP and SpO2 were recorded before induction (baseline value). Since fentanyl is a clear fluid while lornoxicam is yellow, the pharmacist prepared, covered and coded the medications in two coded envelopes for each patient. One envelope containing lornoxicam 8mg (L8), 16 mg (L16) or placebo to be given half an hour before induction of anesthesia and another envelope with fentanyl 100 µg (F) or placebo to be given with induction i.e. each patient received either IV (F), (L8) or (L16).The medications were administered by a different anesthetist, who was not involved in the study. Anesthesia was induced with propofol 2 mg/kg IV followed by cisatracurium 0.15 mg/kg IV to facilitate orotracheal intubation. After tracheal intubation, the patients were ventilated to normocapnia with sevoflurane (2-3% end tidal) in 50% oxygen in air. All patients received IV 1 gm of paracetamol after induction and were monitored with ECG, MAP, SpO2 and EtCO2.  Supplementary fentanyl 0.5 µg/kg was given IV as required in all groups (if > 20% increases in MAP or HR than preinduction values in presence of adequate muscle relaxation). At the end of surgery, muscle relaxation was reversed and extubated.   In the post-anaesthesia care unit (PACU), the time from extubation to spontaneous eye opening was compared between the groups. The patients were monitored with ECG, SpO2, MAP, respiratory rate (RR), VAS and sedation score (0 =awake, 1=mild sedation, 2=sleepy but arousable, and 3 = very sleepy) at 0.5,1, 2, 3 and 4 hours by an anaesthetist, who was not aware of the study drug used. Intramuscular (IM) injection of meperidine 1 mg/kg was administered as a rescue analgesic at VAS > 4. The total amount of meperidine required during first 4 hrs postoperative was recorded. The time of the study drugs injection was recorded after decoding their codes. The first need for rescue analgesic was recorded as the time from the administration of the study-drug and the administration of meperidine. The incidence of PONV or any adverse event was recorded. The PACU staff was not aware of the study drug given. The results were analyzed using SPSS version 16. Sample size was 35 patients for each group in order to detect a 20% change in HR and MAP. The α-error was assumed to be 0.05 and the type II error was set at 0.20. Numerical data were expressed as mean ± SD. The groups were compared with analysis of variances (ANOVA). The VAS pain scores were analyzed by Mann-Whitney U test. Categorical data were compared using the Chi square test. P value of 0.05 was used as the level of significance.  Results 105 patients aged between 18 and 52 yr were enrolled in the study. There were no significant demographic differences between groups (Table 1).  HR and MAP were significantly higher at 10 and 20 minutes after induction of anaesthesia in group L8 compared to groups F and L16 (P < 0.05) (Fig. 1,2). The number of patients with inadequate intra-operative analgesia was significantly higher in group L8 compared to groups F and L16 (Fig 3). In PACU, 40 minutes postoperatively, HR, MAP and VAS were significantly higher in groups F and L8 (Fig 4,5,6). The first analgesic requirement time was significantly longer in group L16 compared to groups F and L8 (Table 2). The mean sedation scores in PACU were insignificantly higher in groups F and L8 compared to group L16 (Table1). While the incidence of PONV was significantly higher in groups F and L8 (p<0.05) (Table 1). Table 1: Demographic characteristics, eye opening time, incidence of postoperative nausea and postoperative sedation score:

Data are expressed as mean ± SD or number of patients* Significant difference (P < 0.05). NS: Non significant.- Time to eye opening is the time from extubation to spontaneous eye opening. Table 2: Perioperative analgesic requirements and time to first postoperative analgesic requirement (mean ± SD)

-Data are expressed as mean ± SD.* Significant difference (P < 0.05). NS: Non significant.-Time of 1st postoperative rescue analgesic is the time elapsed between the administration of the study drug and the administration of an analgesic postoperatively. Fig 1: Intra-operative changes in heart rate in groups Fig 2: Intra-operative changes in MAP in groups Fig 3: Number of patients requested perioperative analgesic supplementation Fig 4: Changes in heart rate in PACU Fig 5: Changes in MAP in PACU: Fig 6: Changes in VAS in PACU Discussion: The use of an opioid, even a short acting one can be associated with adverse effects, which may not be acceptable for patients scheduled for day case surgery. For this reason, it was suggested to substitute an opioid with a non-opioid analgesic for postoperative pain control. The use of a NSAID is associated with adverse effects [1]. Lornoxicam has been successfully used in the prevention and treatment of postoperative pain. It has been shown to be as effective as morphine [4], meperidine [5] and tramadol [6]. To the best of our knowledge, this is the first study to compare the perioperative analgesic efficacy of lornoxicam to fentanyl in patients undergoing day case ENT surgery. We gave Lornoxicam half an hour before induction of anesthesia as the time taken to reach peak plasma concentration (Tmax) was determined to be 0.5 h [7]. During the operative procedure, HR and MAP were significantly higher in group L8 compared to group F and L16. While in PACU, patients in groups F and L8 had higher HR, MAP and VAS score in the early postoperative period compared to patients in group L16. This may be due to inadequate analgesic effect of L8 and the shorter plasma half life of fentanyl compared to L16. The analgesic efficacy of L16 might be attributable to inhibition of cyclo-oxygenase (COX1) and (COX2) activity [2], release of endogenous dynorphin and β-endorphin [5], decrease in peripheral and central prostaglandin production [8] as well as exertion of some of its analgesic activity via the central nervous system [9]. Lornoxicam has a more potent anti-inflammatory and analgesic effect than other oxicams as well as a shorter half life, which decreases the incidence of side effects of drugs with long plasma half life [10]. Arslan and colleagues reported decreased opioid need, PONV and postoperative pain scores when 16 mg of lornoxicam was administered after thyroidectomy [11]. While Xuerong and colleaguessuggested that the increase of postoperative morphine requirements induced by intra-operative administration of fentanyl could be prevented by ketamine or lornoxicam [12].  Rawal reported that NSAIDs are effective as the sole analgesic in a high proportion of cases of mild to moderate pain and it is more convenient to give these drugs by the IV route rather than by IM or rectal administration [13]. The analysis of pain intensity differences was complicated by the fact that many patients postoperatively were asleep at the time their pain assessments were due which may be attributed to effect of opioid and anesthetic medications used. To minimize any missing data we used time to the first dose rescue analgesia (based on changes in hemodynamic data) to evaluate pain intensity differences from baseline. L16 was well tolerated in this study, and was associated with a significantly lower incidence of adverse events than F and L8 which could be due to the opioid side effects in both groups. Norholt and colleaguessupported our results as they reported that, in terms of common acute adverse events, lornoxicam appeared to possess a higher benefit/risk ratio compared with morphine [4]. Zuurmond et al reported that, there is good evidence that avoidance of opioid virtually abolishes the PONV that preclude oral intake of fluids after surgery [14].  In our study, nausea developed in 25.7% of patients in group F, 20% in group L8 but only 8.6% in group L16 who received the least rescue opioid analgesia. Regarding bleeding abnormalities, Hodsman et al reported extensive bleeding required reoperation on two diclofenac group patients submitted to abdominoperitoneal resection of the rectum [15]. In our study no abnormal bleeding was reported by ENT surgeons in any of the study patients. In agreement with our results, Ilias et al[16], Trampitsch et al[17] and Karaman et al [18] used lornoxicam and they did not detect problems with surgical bleeding, bleeding time, blood transfusion requirement or postoperative bleeding.  Stroissnig et al reported that overall, in healthy adult volunteers, oral doses of lornoxicam up to 70 mg have been well tolerated, and there have been no effects on vital signs, urine analysis parameters or clinical serum biochemistry [19]. In our study, none of the patients receiving study drugs experienced severe gastric discomfort, needed rescue antiemetic medication or required admission because of poor pain control.  Previous studies used lornoxicam for reduction of postoperative opioid consumption but none of them had studied the intra-operative use of lornoxicam. So, we selected certain type of surgical procedures which might be suitable to use lornoxicam as a sole intra-operative analgesia. The adjunctive use of acetaminophen may have additive analgesic efficacy to lornoxicam because of its intrinsic opioid-sparing activity. Measurement of serum catecholamine would have been useful. These could be considered as a limitation for the present study. Conclusion:  Intravenous 16 mg lornoxicam with the present study design was comparable to 100 µg fentanyl as intra-operative analgesia but more effective than fentanyl in preventing early postoperative pain in mild to moderate ENT surgical procedures. Intravenous lornoxicam 8 mg was not satisfactory as a sole intra-operative analgesia. The overall incidence of adverse effects of lornoxicam was lower than that of fentanyl.

Case report

We describe a case of a 32 year old primigravida with type III Klippel-Feil Syndrome for an elective Caesarean section. A preanaesthetic assessment at 32^nd week of pregnancy revealed a history of mild asthma for which the patient was on regular salbutamol inhaler. She had no history of cardiovascular or respiratory insufficiency. There was no significant family history. Anaesthetic history included a repair of encephalomyelocele immediately after birth and a squint correction surgery at the age of 6 years under general anaesthesia which was uneventful.

 Examination revealed a woman of small stature, 137 cm in height and weighing 52 kg. Airway examination revealed Mallampati III with a normal mouth opening, a reduced thyromental distance (3 cm) and inability to flex or extend the neck (Figure ¹). She had thoraco-lumbar kyphoscoliosis and examination of the respiratory and cardiovascular system was unremarkable. Electrocardiogram was within normal limits as were haemoglobin, urea and electrolyte estimation. Radiography revealed fusion of atlanto-axial joint (flexion and extension views, Figure ² ) and also fusion of lumbar vertebrae with associated scoliosis (Figure ³Cobb’s angle 25 degree) and Cobb’s angle 25 degree Figure ¹. A 32 year old parturient with Klippel-Feil syndrome with a short webbed neck and severely restricted neck movements  Figure ². Radiograph of a Lateral view of cervical spine showing fusion of atlanto - occipital joint and cervical vertebrae Figure ³. Antero - posterior view of dorsal spine showing deviation of trachea and marked kyphoscoliosis of thoracic spine She was scheduled to have an elective Caesarean section. The anaesthetic management options in this case included either a general anaesthetic with an anticipated difficult endotracheal intubation or a regional anaesthetic. After discussion with the patient, we planned a general anaesthetic technique with awake intubation using a fibreoptic bronchoscope (FOB) as we considered this safe. For FOB through oral route was preferred due to narrow anterior nares. Oral Ranitidine 150 mg was administered as a premedication the night before and on the morning of the planned section. After institution of standard monitoring and securing two peripheral intravenous cannulae (18G & 16 gauges), the upper airway was anaesthetised with nebulisation of 4% Lignocaine (5 ml) and 10% Lignocaine spray to the posterior pharynx. The FOB was passed through the Berman airway by using a ‘spray as you go” technique to anaesthetise the larynx and upper trachea using 4% Lignocaine and keeping well below the toxic dose (3 mg/kg). A 6.5 mm ID endotracheal tube was rail roaded over the FOB prior to its insertion and the airway was successfully secured. Once position of the endotracheal tube was confirmed, anaesthesia was then induced using intravenous Thiopentone 200 mg, Alfentanil 0.5 mg followed by Rocuronium 25 mg. Anaesthesia was maintained using oxygen with nitrous oxide (1:1 ratio) and Sevoflurane (1 MAC). Patient was ventilated with intermittent positive pressure ventilation to maintain normocapnia. The surgery lasted for 45 min and was uneventful. Using a nerve stimulator for assessing neuromuscular blockade she was reversed with Neostigmine 2.5 mg and Glycopyrrolate 0.5 mg towards the end of surgery. The patient was extubated in supine, head-low position when fully awake and in presence of protective airway reflexes. Discussion Klippel-Feil syndrome is an inherited autosomal dominant condition. In 1912, Klippel and Feil ¹ first reported on a patient with a short neck, a low posterior hairline, and severe restriction of neck movements due to complete fusion of the cervical spine. These features now constitute the classic clinical triad which is the hallmark of Klippel-Feil syndrome. A great number of other anomalies associated with Klippel-Feil syndrome may pose a threat to the patient than the obvious deformity of neck. The spinal deformities may cause difficulties with both tracheal intubation and regional anaesthetic techniques. Anaesthetic management may therefore be challenging in these patients. In our case we opted for a general anaesthetic technique rather than a regional technique because of the following reasons: firstly, the patient was not keen to have regional anaesthesia, secondly, it would entail difficulty for regional anaesthesia keeping in view the spinal fusion and scoliosis and thirdly, the dose of a single bolus of spinal anaesthetic would be difficult to judge in this patient and epidural anaesthesia ² might prove technically difficult and is associated with an increased risk of inadvertent dural puncture and poor spread within the epidural space. This patient’s abnormalities posed problems for all the commonly used anaesthetic techniques for Caesarean section. General anaesthesia could be complicated by difficult intubation. While greater use of regional anaesthesia may have reduced the number of deaths due to failed intubation in obstetric practice, several complications of epidural and spinal anaesthesia may still require intubation as part of their management. Some of these include total or high spinal anaesthesia, inadvertent intravascular injection, overdose of local anaesthetic, anaphylaxis and failure. For these reasons, the choice of regional anaesthesia for a patient with known difficult airway does not necessarily bypass the problem of unanticipated intubation. The most commonly associated anomaly in a series of 50 patients from Delaware, USA ³ was scoliosis (60% of cases), renal abnormalities (35%), Sprengel deformity (30%), deafness (30%), synkinesia (20%) and congenital heart disease (14%). The most common heart disease variant was ventricular septal defect. Less commonly associated were ptosis, lateral rectus palsy, facial nerve palsy and upper extremity anomalies. There are 3 variants of Klippel-Feil Syndrome. ⁴ Type I is an extensive abnormality where elements of several cervical and upper thoracic vertebrae are incorporated into a single block. In Type II variant, failure of complete segmentation occurs at one or two cervical interspaces. Type III variant includes Type I or II deformities with coexisting segmentation errors in the lower thoracic or lumbar spine. The incidence of Type II abnormalities was found to be 0.71% of Black and Caucasian skeletons that were between the ages of 17 and 102 years in a study from St Louis, Missouri, USA ⁵ and it is considered to be the most common form. C₂-₃ and C₅-₆ are the interspaces usually involved. It often remains unrecognised since the neck may appear normal and the patients are asymptomatic until later in life, when they present due to their increased susceptibility to cervical osteo-arthritis. Patients with Type I abnormalities are 50 times less common than Type II but are reported more frequently. This is probably because they exhibit the classic triad and thus have bizarre appearances. ⁶ These patients are frequently disabled by birth injuries, or have major anomalies in other organ systems. A planned elective section at term was considered as the best option for delivery of the baby by the obstetricians due to severe cephalo-pelvic disproportion and also due to anaesthetic issues regarding management. The case was managed successfully with a favourable outcome both for the mother and the baby.

Procedural operations, are procedures outside the operating room, which developed from a facilitation of diagnostic and therapeutic procedures into an independent subspecialty. Procedural sedation and analgesia is a minimally depressed level of consciousness that retains the patient's ability to maintain a patent airway independently and continuously⁽¹⁾.

Propofol is a short-acting intravenous sedative agent used for the induction and maintenance of general anesthesia for adults and children, sedation for intubated, mechanically ventilated adults in Intensive Care Units (ICU), and in procedures such as colonoscopy. It provides no analgesia(2). Ketamine is classified as an NMDA receptor antagonist and has also been found to bind to opioid receptors and sigma receptors. It induces a state referred to as "dissociative anesthesia"(3).

Ketofol (ketamine/propofol combination) was used for procedural sedation and analgesia. Ketamine and propofol are physically compatible for 1 hr at 23^oC with no increase in particle content at Y site injection ⁽⁴⁾. Ketamine and propofol administered in combination have offered effective sedation for spinal anesthesia and for gynecologic, ophthalmologic, and cardiovascular procedures in all age groups. The opposing hemodynamic and respiratory effects of each drug may enhance the utility of this drug combination, increasing both safety and efficacy and allowing reduction in the dose of propofol required to achieve sedation.

However, evaluation of the effectiveness of different concentrations of Ketofol in procedural operation regarding changes in hemodynamic, emergence phenomena, recovery time, the doses, and adverse effects was not yet studied, so this randomized, double blinded study was designed to compare the quality of analgesia and side effects of intravenous different concentrations of ketofol in children scheduled for procedural operations.

Methods:

A hundred patients, American Society of Anesthesia (ASA) class I or II scheduled for procedural operation, ages 3 to 12 years were enrolled in this study. After obtaining approval from the local research ethics committee, all patients and their parents were informed about the procedure and the anesthetic technique and an informed written consent was obtained from each. Patients with clinically significant cardiovascular, respiratory, hepatic diseases or epileptic patients, longer procedures more than one hour and sensitivity to the drugs were excluded from the study.

Patients were randomized into two equal groups each of 50 patients going for procedural operation, e.g. esophgoscopy, rectoscopy, bone marrow aspiration and liver biopsy. Pre procedural visit was done to evaluate if that patient fulfils the criteria of study and for fasting instruction. In the preoperative waiting area, an IV catheter was placed after applying emla cream. Baseline measurements included Non Invasive Blood Pressure (NIBP), heart rate, respiratory rate, and pain faces scale which is recommended for children aged 3 years and older (Fig1)⁽⁵⁾. The level of sedation was determined by Ramsay Sedation Scale⁽⁶⁾. A separate observer who was blind to the drug combination being used assessed the depth of sedation of such patients.

Fig 1: Pain Faces Scale.

A propofol/ketamine admixture was prepared by an assistant who was not involved in the clinical management of the study patients. According to a prestudy randomization schedule of study group assignment, a ketofol (1:1): propofol 14.285 mg, ketamine 14.285 mg/ml by mixing 10 ml propofol 2% (20 mg/ml) with 4 ml ketamine (50 mg/ml) in group I, while in group II ketofol (4:1): propofol 18.1818 mg , ketamine 4.5454 mg/ml by mixing 10 ml propofol 2% (20 mg/ml) with 1 ml ketamine (50 mg/ml).

Both bolus and maintenance doses were given using syringe pump (B/Braun). Set up for delivery of Ketofol in both groups as an initial bolus of 600 g/kg IV (calculated as dose of propofol in these infusions for simplicity), followed by an initial maintenance infusion at 100 g/kg/min by anesthetist who was blinded to the identity of study infusion.The level of sedation was assessed at 1- 3 minutes intervals, and the initial infusion rate was adjusted (in 25 g/kg/min increments) to achieve Ramsay Sedation Scale of 5 before starting the procedure.

During the procedure, patients were kept on oxygen nasal prongs with a CO₂ sampling port. All patients were monitored with NIBP, electrocardiography (ECG), Pulse oximetry(SpO₂₎, heart rate (HR), and end tidal carbondioxide( EtCO₂₎. The measurement started before commencement of the intravenous (IV) line and continued five minutes after induction. The patients were also assessed for apnoea, which was defined as the loss of respiratory efforts for more than 20 seconds or fall of SpO₂ below 95%. Complaints of pain/discomfort were treated by an incremental increase in the study drug infusion rate.

The study drug infusion was discontinued at the end of the surgical procedure, and the total drug requirements were noted. After the completion of the procedure, patients were transferred to recovery room when an Aldrete score⁽⁷⁾ 9-10 was confirmed, and kept there till ready for discharge. The recovery room nurses were blinded to the study medication received by the patients. The incidence of any episode of postoperative nausea and vomiting (PONV) or any other side effects (e.g. hallucinations, agitation or pain) was noted. The patients vital signs were assessed at 5-min intervals. Patients were considered "ready for discharge" when they had stable vital signs, oriented, able to ambulate unassisted, had no intractable nausea or vomiting, and had minimal pain. Discharge times were determined from the time the study drug infusion was discontinued. Outpatients were given written discharge instructions regarding post-procedure precautions and a telephone number to use in case of emergency.

Descriptive variables were analyzed using Students t-test and X² test as appropriate using SPSS software statistical computer package version 15. Differences between the groups in mean blood pressure (BP),heart rate( HR), end-tidalCO₂, oxygen saturation and ketofol requirements were compared using analysis of variance with repeated measures. A P value < 0.05 was considered to be statistically significant. Values are expressed as meanSD.

Results:

There were no significant differences among patients in both groups regarding number of patients, age, sex, weight, ASA physical status, and duration of ketofol infusion (table 1). There was 2 patients excluded in group I; one had a history of epilepsy and the other was acute lymphocytic leukemia on corticosteroids, while in group II only one patient was excluded due to history of epilepsy (Table 1).

Sedation scores were similar in both groups. The average ketofol initial dose in group I was 600 g /kg followed by an average infusion rate of 116 24 g/kg/min, while in group II the average ketofol initial dose was 600 g/Kg followed by an average infusion rate of 132 36 g/kg/min with a significant difference between groups (P <0.05).

There was a minimal decrease in mean arterial blood pressure (MAP) from baseline in both groups following the initial dose of ketofol. Significant hypotension was noted in 2 patients in group I (4%) and in 3 patients in group II (6%) which was corrected by a bolus of Ringers solution 10 ml/kg IV. The diffrence between the groups was statistically insignificant . All the patients had increase in pulse rate compared to the baseline. The change was least in group II (p <0.05), but no patient had severe tachycardia requiring treatment in both groups.

There was increase in Etco₂ in both groups after induction with statistically insignificant difference between groups. Patients in both groups had decrease in arterial oxygen saturation (SpO₂) after induction. Five patients (10%) in group I and three patients (6%) in group II had apnea and hypoxia after induction (SpO₂ <95%). Excessive salivation was noted in 15 patients (31%) in group I but only two patients (4%) in group II. Eight patients (16%) in group I and two patients (4%) in group II experienced airway obstruction or apnea which required airway support. These changes were statistically significant between both groups.

Table 1. Demographic Characteristics, Intraoperative Management, and Recovery Times of Patients in the Study Groups

Two patients in group II (4%) and one patient in group I (2%) had pain and discomfort during the procedure which was overcome by incremental boluses of infusions. In group I, one patient (2%) complained of postoperative nausea, four patients (8%) experienced bad dreams and hallucinations and five patients (10%) complained of agitations with no psychomimetic changes in group II

The time to ambulation in group I and II patients was 15.4 9.5 and 8.2 6.7 minutes respectively, while readiness to discharge was 26.5 11.3 in group I and 15.3 8.4 minutes in group II. The time to actual discharge was 38.8 13.5 minutes in group I and 28.2 8.9 minutes in group II. These changes in recovery timings were statistically significant.

Discussion:

The goals of procedural sedation are to provide an adequate level of sedation while minimizing pain and anxiety, maximizing amnesia, minimizing the potential for adverse drug-related events, controlling behavior, and maintaining a stable cardiovascular and respiratory status. A number of studies have demonstrated that the combination of ketamine and Propofol (ketofol) for sedation is safe and effective. The combination of the two agents appears to reduce side effects of each medication used alone, and allows for a rapid recovery time⁽¹⁾.

We compared the safety and efficacy of different concentrations of ketofol in procedural operations in children. The rate of ketofol infusion in group II was higher than in group I due to due to incremental doses of ketofol given to get the desired depth of sedation and abort pain sensation which was due to less ketamine content in such infusion compared to group I. Propofol in the recommended dose of 2-2.5 mg/kg almost always causes fall in blood pressure and the extent of fall depends upon the dose and adjuvant drugs used. Because we used an initial infusion dose of only 600 g/kg, the fall in MAP was mild (6%) and similar in both groups. The induction doses of propofol are reduced considerably by combination with small doses of ketamine. Ketamine had the additional advantage of better hemodynamic stability. Our results are consistent with Furuya et al and Hui et al who suggested that the minimal change observed in arterial pressure may be dose related and also because sympathomimetic actions of ketamine were effective in counter-acting the hemodynamic depression of propofol. There was a trend for pulse rate to increase after the induction in all the groups, but there was no occurrence of profound tachycardia in any group^(8,9).

Akin et al published a trial of 60 patients between one month and 13 years of age undergoing cardiac catheterization who received sedation with propofol or propofol plus ketamine (3:1). They found a significant (decrease in MAP in 11 patients in the propofol monotherapy group and three patients in the ketofol group. They concluded that the addition of low-dose ketamine to propofol preserved MAP without prolonging recovery or increasing the incidence of adverse events⁽¹⁰⁾. While, Goh et al published a 90 patients having a laryngeal mask airway (LMA) placed received propofol with either ketamine (5:1), fentanyl (1 g /kg), or placebo normal saline. They found the ketofol group had a significantly higher systolic blood pressure than the other two groups. They concluded that ketofol provided equivalent LMA insertion conditions while maximizing hemodynamics and minimizing apnea⁽¹¹⁾.

End-tidal CO₂ increased slightly after induction in both groups. In agreement with our results, Mildh et al and Persson et al who reported that ketamine-induced sympathoadrenal activation may account for improved ventilation, also arousal secondary to the subjective side effects of ketamine (e.g., perceptual changes and anxiety) may also contribute ^(12,13). Also our results have confirmed the previous reports of Frey et al and Badrinath et al ^(14,15), suggesting that the combination of a small-dose ketamine with propofol improves ventilation during sedation.

We expect that the apnea and desaturation recorded in group I (10%) was due to the excessive salivation complicated the higher dose of ketamine in this group which led to impaired breathing and required airway support in 16% of such patients. While apnea and desaturation which happened in group II could be due to the higher infusion rate of propofol in ketofol combination.

Willman and Andolfatto published a study of 114 patients requiring procedural sedation and analgesia mainly for orthopedic procedures were given a 1:1 mixture of propofol and ketamine. Transient hypoxia occurred in 2.6% of patients, out of them one patient required bag valve mask ventilation. Three patients had an emergence reaction, one of whom received midazolam. No patient had vomiting or aspiration. Procedural success rate in this study without the use of adjunctive medications was 96.5%. Median time until recovery was 15 minutes (range 5 to 45 minutes) ⁽¹⁶⁾. Furthermore, Akin et al compared propofol to propofol plus ketamine (3:1) in 60 patients between one and 13 years of age undergoing auditory brainstem response testing. There were no cases of desaturation in the ketofol group, but in the propofol group 4/30 experienced desaturation and 6/30 had apnea. The authors concluded that the addition of low dose ketamine to propofol reduced the risk of respiratory depression and the need for repeat medication administration⁽¹⁷⁾.

The incidence of clinically significant psychotomimetic effects was noted in the large-dose ketamine group (group I). This could be a dose-dependent interaction of the excitatory anesthetic ketamine with a pure central nervous system depressant, such as propofol ^(18,19). There were no post procedural psychotomimetic symptoms recorded in group II. In addition, the patients mood was significantly better in the recovery room and cognitive function recovered more rapidly in such group than those given higher dose of ketamine. Nagata et al and Mortero et al are coinciding with our results as they suggested that ketamine in sedative doses is associated with electroencephalographic activation. Furthermore, small-dose ketamine increases thalamic sensory output and arousal. Sedative effects of propofol may be partially antagonized by the arousal effects of ketamine^(20,21). While Akin et al in a trial of 40 adult patients undergoing endometrial biopsy, reported that the combination of propofol (1 mg/kg) plus fentanyl (1 g/kg) was compared to the combination of propofol plus ketamine (2:1). Time to recovery was similar; however time to discharge was longer in the ketofol group secondary to the increased presence of adverse events including nausea, vertigo, and visual disturbances. These authors concluded that although both regimens seem safe, ketofol (2:1) had more adverse events leading to a longer time until discharge and had a lower overall patient satisfaction⁽²²⁾.

Badrinath et al, published One hundred female outpatients undergoing breast biopsy procedures under local anesthesia received an infusion of a solution containing propofol in combination with different doses of ketamine . The sedative infusion rate was varied to maintain a deep level of sedation and normal respiratory and hemodynamic functions. They reported that combination of propofol and ketamine (5:1) provides effective sedation/analgesia during monitored anesthesia care⁽¹⁵⁾. Our results suggest that our combination propofol and ketamine (4:1) was more suitable in procedural operations as Badrinath et al used their preferred combination (5:1) only in monitored anesthesia care and they supplement their sedation with local anesthesia infiltration.

In conclusion, propofol combined with ketamine (4:1) infusion for procedural operations contributed adequate sedation and analgesia without hemodynamic and respiratory depression or psychotomimetic side effects and appears to be a safe and useful technique for procedural operations in the ambulatory setting.

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