Category Archives: PHARM

Prehospital and Retrieval Medicine

Intranasal ketamine for kids – 1mg / kg?

A small pilot study on a convenience sample of children presenting to the emergency department with acute limb injury pain evaluated the use of intranasal ketamine(1).
Initial dose averaged 0.84 mg/kg and a third of the patients required a top up dose at 15 minutes, resulting in a total dose of about 1.0 mg/kg to provide adequate analgesia by 30 min for most patients. The authors suggest that this could guide investigators on an appropriate dose of IN ketamine for use in clinical trials.
Adverse events were all transient and mild.
Prior to administration, the ketamine was diluted with saline to a total volume of 0.5 mL and was administered as 0.25 mL per nare using a Mucosal Atomiser Device (MAD, Wolfe Tory Medical, Salt Lake City, UT, USA). According to the protocols in my Service, this device requires 0.1 ml to prime its dead space(2). It is unclear whether this factor may have affected the total dose delivered to the patient in this study.
1. Sub-dissociative dose intranasal ketamine for limb injury pain in children in the emergency department: A pilot study
Emerg Med Australas. 2013 Apr;25(2):161-7
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OBJECTIVE: The present study aims to conduct a pilot study examining the effectiveness of intranasal (IN) ketamine as an analgesic for children in the ED.

METHODS: The present study used an observational study on a convenience sample of paediatric ED patients aged 3-13 years, with moderate to severe (≥6/10) pain from isolated limb injury. IN ketamine was administered at enrolment, with a supplementary dose after 15 min, if required. Primary outcome was change in median pain rating at 30 min. Secondary outcomes included change in median pain rating at 60 min, patient/parent satisfaction, need for additional analgesia and adverse events being reported.

RESULTS: For the 28 children included in the primary analysis, median age was 9 years (interquartile range [IQR] 6-10). Twenty-three (82.1%) were male. Eighteen (64%) received only one dose of IN ketamine (mean dose 0.84 mg/kg), whereas 10 (36%) required a second dose at 15 min (mean for second dose 0.54 mg/kg). The total mean dose for all patients was 1.0 mg/kg (95% CI: 0.92-1.14). The median pain rating decreased from 74.5 mm (IQR 60-85) to 30 mm (IQR 12-51.5) at 30 min (P < 0.001, Mann-Whitney). For the 24 children who contributed data at 60 min, the median pain rating was 25 mm (IQR 4-44). Twenty (83%) subjects were satisfied with their analgesia. Eight (33%) were given additional opioid analgesia and the 28 reported adverse events were all transient and mild.
CONCLUSIONS: In this population, an average dose of 1.0 mg/kg IN ketamine provided adequate analgesia by 30 min for most patients

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2. Case report: prehospital use of intranasal ketamine for paediatric burn injury
Emerg Med J. 2011 Apr;28(4):328-9
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In this study, the administration of an intravenous ketamine formulation to the nasal mucosa of a paediatric burn victim is described in the prehospital environment. Effective analgesia was achieved without the need for vascular or osseous access. Intranasal ketamine has been previously described for chronic pain and anaesthetic premedication. This case highlights its potential as an option for prehospital analgesia.

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Another argument for ED thoracotomy

ICM-iconA team from Los Angeles (including the great Kenji Inaba) has published a study on penetrating cardiac wounds in the pediatric population[1]. This is one of the largest studies on this thankfully rare event.
The outcome was poor which may be due to the high proportion of patients arriving at hospital without signs of life (SOL).
What I like about the paper is the discussion of their liberal policy for the use of resuscitative ED thoracotomy:


…we do not rely heavily on prehospital data regarding the precise timing of loss of SOL. Thus, at the discretion of the attending trauma surgeon, every penetrating injury to the chest with SOL lost during patient transport will be considered for ED thoracotomy.

In cases when a perfusing cardiac rhythm is regained, the patient will receive all operative and critical care support as standard of care. If the patient progresses to brain death, aggressive donor management will be implemented in accordance with consent obtained by the organ procurement organization.

In a recent publication, we observed two pediatric patients who underwent ED thoracotomy that subsequently became organ donors after brain death was declared [2]. A total of nine organs were recovered for transplantation. This contemporary outcome measure is of paramount importance in the current era of significant organ shortage.

When such aggressive resuscitative procedures are attempted on arrested trauma patients, there is a temptation to justify inaction on the grounds of futility or the risk of ‘creating a vegetable’. This paper reminds us that other outcome benefits may arise from attempted resuscitation even if the patient does not survive.

These benefits include the saving of other lives through organ donation. In addition to this, there is the opportunity for family members to be with their loved one on the ICU, to hold their warm hand for the last time, to hear the news broken by a team they have gotten to know and trust, to enact any spiritual or religious rites that may provide a source of comfort and closure, and to be there during withdrawal of life sustaining therapies after diagnosis of brain stem death. That will never be pleasant, but on the bleak spectrum of parental torture it may be better than being told the devastating news in the ED relatives’ room by a stranger they’ve never met but will remember forever.

The ED thoracotomy may at the very least remove any doubt that everything that could have been done, was done.
1. Penetrating cardiac trauma in adolescents: A rare injury with excessive mortality
Journal of Pediatric Surgery (2013) 48, 745–749
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Background Penetrating cardiac injuries in pediatric patients are rarely encountered. Likewise, the in-hospital outcome measures following these injuries are poorly described.

Methods All pediatric patients (<18years) sustaining penetrating cardiac injuries between 1/2000 and 12/2010 were retrospectively identified using the trauma registry of an urban level I trauma center. Demographic and admission variables, operative findings, and hospital course were extracted. Outpatient follow-up data were obtained through chart reviews and cardiac-specific imaging studies.

Results During the 11-year study period, 32 of the 4569 pediatric trauma admissions (0.7%) sustained penetrating cardiac injuries. All patients were male and the majority suffered stab wounds (81.2%). The mean systolic blood pressure on admission was 28.8±52.9mmHg and the mean ISS was 46.9±27.7. Cardiac chambers involved were the right ventricle (46.9%), the left ventricle (43.8%), and the right atrium (18.8%). Overall, 9 patients (28.1%) survived to hospital discharge. Outpatient follow-up echocardiography was available for 4 patients (44.4%). An abnormal echocardiography result was found in 1 patient, demonstrating hypokinesia and tricuspid regurgitation.

Conclusions Penetrating cardiac trauma is a rare injury in the pediatric population. Cardiac chambers predominantly involved are the right and left ventricles. This injury is associated with a low in-hospital survival (<30%).

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2. Organ donation: an important outcome after resuscitative thoracotomy
J Am Coll Surg. 2010 Oct;211(4):450-5
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BACKGROUND: The persistent shortage of transplantable organs remains a critical issue around the world. The purpose of this study was to investigate outcomes, including organ procurement, in trauma patients undergoing resuscitative emergency department thoracotomy (EDT). Our hypothesis was that potential organ donor rescue is one of the important outcomes after traumatic arrest and EDT.

STUDY DESIGN: Retrospective study at Los Angeles County and University of Southern California Medical Center. Patients undergoing resuscitative EDT from January 1, 2006 through June 30, 2009 were analyzed. Primary outcomes measures included survival. Secondary outcomes included organ donation and the brain-dead potential organ donor.

RESULTS: During the 42-month study period, a total of 263 patients underwent EDT. Return of a pulse was achieved in 85 patients (32.3%). Of those patients, 37 (43.5%) subsequently died in the operating room and 48 (56.5%) survived to the surgical intensive care unit. Overall, 5 patients (1.9%) survived to discharge and 11 patients (4.2%) became potential organ donors. Five of the 11 potential organ donors had sustained a blunt mechanism injury. Of the 11 potential organ donors, 8 did not donate: 4 families declined consent, 3 because of poor organ function, and 1 expired due to cardiopulmonary collapse. Eventually 11 organs (6 kidneys, 2 livers, 2 pancreases, and 1 small bowel) were harvested from 3 donors. Two of the 3 donors had sustained blunt injury and 1 penetrating mechanism of injury.

CONCLUSIONS: Procurement of organs is one of the tangible outcomes after EDT. These organs have the potential to alter the survival and quality of life of more recipients than the number of survivors of the procedure itself.

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Identifying the febrile kid who's too tachypnoeic

Body temperature raises heart rate and respiratory rate in kids, potentially affecting our interpretation of these clinical signs.
Dutch investigators developed centile charts of respiratory rates for specific body temperatures (derivation study), so that abnormally high rates could be identified as a means of predicting lower respiratory infection (validation set).
Respiratory rate increased overall by 2.2 breaths/min per 1°C rise (standard error 0.2) after accounting for age and temperature in the model, which is similar to a previous UK study that suggested a rise in respiratory rate of around 0.5-2 breaths per minute and an increase in heart rate of about 10 beats per minute for every 1 degree celcius above normal.
Cut-off values at the 97th centile were more useful in detecting the presence of LRTI than existing (Advanced Paediatric Life Support) respiratory rate thresholds.
The respiratory rate charts are available here.
Derivation and validation of age and temperature specific reference values and centile charts to predict lower respiratory tract infection in children with fever: prospective observational study
BMJ. 2012 Jul 3;345:e4224
Free Full Text Link

Lateral chest thrusts for choking

An interesting animal study examined the techniques recommended in basic choking management algorithms for foreign body airway obstruction (chest and abdominal thrusts). In terms of the pressures generated, lateral chest thrusts were the most effective, although they are not recommended in current guidelines.
The technique described (on intubated pigs) was:


The animals were placed on the floor and on their side. The lower (dependent) side of the chest was braced by the ground and thrust was applied to the upper part of the upper side by two hands side by side with the higher one just below the axilla.

Interestingly – and I didn’t know this (although perhaps should have!) – the Australian Resuscitation Council (ARC) recommended lateral chest thrusts instead of abdominal thrusts for over 20 years.
While we should always exercise extreme caution in extrapolating animal studies to humans, this makes me want to consider lateral thrusts in the first aid (ie. no equipment) situation if other measures are failing.
Lateral versus anterior thoracic thrusts in the generation of airway pressure in anaesthetised pigs
Resuscitation. 2013 Apr;84(4):515-9
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Objective Anterior chest thrusts (with the subject sitting or standing and thrusts applied to the lower sternum) are recommended by the Australian Resuscitation Council as part of the sequence for clearing upper airway obstruction by a foreign body. Lateral chest thrusts (with the victim lying on their side) are no longer recommended due to a lack of evidence. We compared anterior, lateral chest and abdominal thrusts in the generation of airway pressures using a suitable animal model.

Methods This was a repeated-measures, cross-over, clinical trial of eight anaesthetised, intubated, adult pigs. For each animal, ten trials of each technique were undertaken with the upper airway obstructed. A chest/abdominal pressure transducer, a pneumotachograph and an intra-oesophageal balloon catheter recorded chest/abdominal thrust, expiratory air flows, airway and intrapleural pressures, respectively.

Results The mean (SD) thrust pressures generated for the anterior, lateral and abdominal techniques were 120.9 (11.0), 135.2 (20.0), and 142.4 (27.3) cmH2O, respectively (p < 0.0001). The mean (SD) peak expiratory airway pressures were 6.5 (3.0), 18.0 (5.5) and 13.8 (6.7) cmH2O, respectively (p < 0.0001). The mean (SD) peak expiratory intrapleural pressures were 5.4 (2.7), 13.5 (6.2) and 10.3 (8.5) cmH2O, respectively (p < 0.0001). At autopsy, no rib, intra-abdominal or intra-thoracic injury was observed.
Conclusion Lateral chest and abdominal thrust techniques generated significantly greater airway and pleural pressures than the anterior thrust technique. We recommend further research to provide additional evidence that may inform management guidelines for clearing foreign body upper airway obstruction.

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Save a life by watching telly?

BB2.055If you’re in the United Kingdom on Thursday 21st March please consider watching BBC’s Horizon program at 9pm on BBC2.
I’m in Australia so I’ll miss it, but I’m moved by the whole background to this endeavour and really want you to help me spread the word.
Many of you will be familiar with the tragic case of Mrs Elaine Bromiley, who died from hypoxic brain injury after clinicians lost control of her airway during an anaesthetic for elective surgery. Her husband Martin has heroically campaigned for a greater awareness of the need to understand human factors in healthcare so such disasters can be prevented in the future.
Mr Bromiley describes the program, which is hosted by intensivist and space medicine expert Dr Kevin Fong:


Kevin and the Horizon team have produced something inspirational yet scientific, and – just as importantly – it’s by a clinician, for clinicians. It’s written in a way that will appeal to both those in healthcare and the public. It uses a tragic death to highlight human factors that all of us are prone to, and looks at how we can learn from others both in and outside healthcare to make a real difference in the future.

The lessons of this programme are for everyone in healthcare.

It would be wonderful if you could pass on details of the programme to anyone you know who works in healthcare. My goal is that by the end of this week, every one of the 1 million or so people who work in healthcare in the UK will be able to watch it (whether on Thursday or on iPlayer).


From the Health Foundation blog

Please help us reach this 1000 000 viewer target by watching on Thursday or later on iPlayer. Tweet about it or forward this message to as many healthcare providers you know. Help Martin help the rest of us avoid the kind of tragedy that he and his children have so bravely endured.
For more information on Mrs Bromiley’s case, watch ‘Just a Routine Operation’:


Cliff

Traumatic cardiac arrest outcomes

simEver heard anyone spout dogma along the lines of: “it’s a traumatic cardiac arrest – resuscitation is futile as the outcome is hopeless: survival is close to zero per cent”?
I have. Less frequently in recent years, I’ll admit, but you still hear it spout forth from the anus of some muppet in the trauma team. Here’s some recent data to add to the existing literature that challenges the ‘zero per cent survival’ proponents. A Spanish study retrospectively analysed 167 traumatic cardiac arrests (TCAs). 6.6% achieved a complete neurological recovery (CNR), which increased to 9.4% if the first ambulance to arrive contained an advanced team including a physician. Rhythm and age were important: CNR was achieved in 36.4% of VFs, 7% of PEAs, and 2.7% of those in asystole; survival rate by age groups was 23.1% in children, 5.7% in adults, and 3.7% in the elderly.
Since traumatic arrest tends to affect a younger age group than medical arrests, the authors suggest:
Avoiding the potential decrease in life expectancy in this kind of patient justifies using medical resources to their utmost potential to achieve their survival
Since 2.7% of the asystolic patients achieved a CNR, the authors challenge the practice proposed by some authors that Advanced Life Support be withheld in TCA patients with asystole as the initial rhythm:
had that indication been followed, three of our patients who survived neurologically intact would have been declared dead on-scene.”
I’d like to know what interventions were making the difference in these patients. They describe what’s on offer as:


In our EMS, all TCA patients receive ALS on-scene, which includes intubation, intravenous access, fluid and drug therapy, point-of-care blood analysis, and procedures such as chest drain insertion, pericardiocentesis, or Focused Assessment with Sonography for Trauma ultrasonography to improve the treatment of the cause of the TCA.

It appears that crystalloids and colloids are their fluid therapy of choice; unlike many British and Australian physician-based prehospital services they made no mention of the administration of prehospital blood products.
Traumatic cardiac arrest: Should advanced life support be initiated?
J Trauma Acute Care Surg. 2013 Feb;74(2):634-8
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BACKGROUND: Several studies recommend not initiating advanced life support in traumatic cardiac arrest (TCA), mainly owing to the poor prognosis in several series that have been published. This study aimed to analyze the survival of the TCA in our series and to determine which factors are more frequently associated with recovery of spontaneous circulation (ROSC) and complete neurologic recovery (CNR).

METHODS: This is a cohort study (2006-2009) of treatment benefits.

RESULTS: A total of 167 TCAs were analyzed. ROSC was obtained in 49.1%, and 6.6% achieved a CNR. Survival rate by age groups was 23.1% in children, 5.7% in adults, and 3.7% in the elderly (p < 0.05). There was no significant difference in ROSC according to which type of ambulance arrived first, but if the advanced ambulance first, 9.41% achieved a CNR, whereas only 3.7% if the basic ambulance first. We found significant differences between the response time and survival with a CNR (response time was 6.9 minutes for those who achieved a CNR and 9.2 minutes for those who died). Of the patients, 67.5% were in asystole, 25.9% in pulseless electrical activity (PEA), and 6.6% in VF. ROSC was achieved in 90.9% of VFs, 60.5% of PEAs, and 40.2% of those in asystole (p < 0.05), and CNR was achieved in 36.4% of VFs, 7% of PEAs, and 2.7% of those in asystole (p < 0.05). The mean (SD) quantity of fluid replacement was greater in ROSC (1,188.8 [786.7] mL of crystalloids and 487.7 [688.9] mL of colloids) than in those without ROSC (890.4 [622.4] mL of crystalloids and 184.2 [359.3] mL of colloids) (p < 0.05).

CONCLUSION: In our series, 6.6% of the patients survived with a CNR. Our data allow us to state beyond any doubt that advanced life support should be initiated in TCA patients regardless of the initial rhythm, especially in children and those with VF or PEA as the initial rhythm and that a rapid response time and aggressive fluid replacement are the keys to the survival of these patients.

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The importance of first pass success

mv-vl-iconA large single-centre study in an academic tertiary care center emergency department (where residents perform most of the intubations) examined 1,828 orotracheal intubations, of which 1,333 were intubated successfully on the first attempt (72.9%).
Adverse events (AE) captured were oesophageal intubation, oxygen desaturation, witnessed aspiration, mainstem intubation, accidental extubation, cuff leak, dental trauma, laryngospasm, pneumothorax, hypotension, dysrhythmia, and cardiac arrest.
When the first pass was successful, the incidence of AEs was 14.2%. More than one attempt was associated with significantly more AEs. Patients requiring two attempts had 33% more AEs (47.2%) and as the number of attempts increased, so did the risk of AEs, with the largest increase in AEs occurring between an unsuccessful first attempt and the second intubation attempt.
This is a powerful argument in favour of optimising first pass success. In the prehospital service I work for, We like to include this in a ‘first pass, no desat, no hypotension’ package that includes team simulation training, pre-intubation briefing, checklist use, optimisation of position, ketamine induction (and avoidance of propofol), apnoeic oxygenation, bougie use, bimanual laryngoscopy, and waveform capnography.
The Importance of First Pass Success When Performing Orotracheal Intubation in the Emergency Department
Academic Emergency Medicine 2013;20(1):71–78, Free Full Text
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Objectives The goal of this study was to determine the association of first pass success with the incidence of adverse events (AEs) during emergency department (ED) intubations.

Methods This was a retrospective analysis of prospectively collected continuous quality improvement data based on orotracheal intubations performed in an academic ED over a 4-year period. Following each intubation, the operator completed a data form regarding multiple aspects of the intubation, including patient and operator characteristics, method of intubation, device used, the number of attempts required, and AEs. Numerous AEs were tracked and included events such as witnessed aspiration, oxygen desaturation, esophageal intubation, hypotension, dysrhythmia, and cardiac arrest. Multivariable logistic regression was used to assess the relationship between the primary predictor variable of interest, first pass success, and the outcome variable, the presence of one or more AEs, after controlling for various other potential risk factors and confounders.

Results Over the 4-year study period, there were 1,828 orotracheal intubations. If the intubation was successful on the first attempt, the incidence of one or more AEs was 14.2% (95% confidence interval [CI] = 12.4% to 16.2%). In cases requiring two attempts, the incidence of one or more AEs was 47.2% (95% CI = 41.8% to 52.7%); in cases requiring three attempts, the incidence of one or more AEs was 63.6% (95% CI = 53.7% to 72.6%); and in cases requiring four or more attempts, the incidence of one or more AEs was 70.6% (95% CI = 56.2.3% to 82.5%). Multivariable logistic regression showed that more than one attempt at tracheal intubation was a significant predictor of one or more AEs (adjusted odds ratio [aOR] = 7.52, 95% CI = 5.86 to 9.63).

Conclusions When performing orotracheal intubation in the ED, first pass success is associated with a relatively small incidence of AEs. As the number of attempts increases, the incidence of AEs increases substantially.

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Alternative 'universal' plasma donor

The group usually considered the universal donor for fresh frozen plasma because it contains no anti-A or anti-B antibodies is Type AB. Due to its limited availability the trauma service of the Mayo Clinic in Minnesota has been issuing thawed group A plasma to its flight crews who retrieve major trauma casualties from rural centres. This is given with packed group O red cells to patients who meet their prehospital massive transfusion protocol criteria. Some patients will inevitably receive ABO-incompatible plasma (namely patients with Group B or AB blood) which could theoretically give rise to haemolytic transfusion reactions, in which donor antibodies bind host red cells, activate complement, and give rise to anaemia, disseminated intravascular coagulation, acute kidney injury, and death. However:

  • the transfusion of platelets containing ABO-incompatible plasma is common, with up to 2 units of incompatible plasma per apheresis platelet unit, whereas haemolytic reactions to platelets are rare (1 in 9,000 incompatible platelet transfusions);
  • all reports of haemolytic reactions are caused by products that contain Group O plasma and there has never been a documented case of haemolysis as a result of products containing Group A plasma

A retrospective review showed no increased rates of adverse events with Type A compared with AB or ABO-compatible plasma. Since only a small absolute number of patients received an ABO-incompatible plasma transfusion, it could be argued that the study is underpowered (a point acknowledged by the authors). However this is very important and useful information for resource-limited settings.
Emergency use of prethawed Group A plasma in trauma patients
J Trauma Acute Care Surg. 2013 Jan;74(1):69-74
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BACKGROUND: Massive transfusion protocols lead to increased use of the rare universal plasma donor, Type AB, potentially limiting supply. Owing to safety data, with a goal of avoiding shortages, our blood bank exploited Group A rather than AB for all emergency release plasma transfusions. We hypothesized that ABO-incompatible plasma transfusions had mortality similar to ABO-compatible transfusions.

METHODS: Review of all trauma patients receiving emergency release plasma (Group A) from 2008 to 2011 was performed. ABO compatibility was determined post hoc. Deaths before blood typing were eliminated. p < 0.05 was considered statistically significant.

RESULTS: Of the 254 patients, 35 (14%) received ABO-incompatible and 219 (86%) received ABO-compatible transfusions. There was no difference in age (56 years vs. 59 years), sex (63% vs. 63% male), Injury Severity Score (ISS) (25 vs. 22), or time spent in the trauma bay (24 vs. 26.5 minutes). Median blood product units transfused were similar: emergency release plasma (2 vs. 2), total plasma at 24 hours (6 vs. 4), total red blood cells at 24 hours (5 vs. 4), plasma-red blood cells at 24 hours (1.3:1 vs. 1.1:1), and plasma deficits at 24 hours (2 vs. 1). Overall complications were similar (43% vs. 35%) as were rates of possible transfusion-related acute lung injury (2.9% vs. 1.8%), acute lung injury (3.7% vs. 2.5%), adult respiratory distress syndrome (2.9% vs. 1.8%), deep venous thrombosis (2.9% vs. 4.1%), pulmonary embolism (5.8% vs. 7.3%), and death (20% vs. 22%). Ventilator (6 vs. 3), intensive care unit (4 vs. 3), and hospital days (9 vs. 7) were similar. There were no hemolytic reactions. Mortality was significantly greater for the patients who received incompatible plasma if concurrent with a massive transfusion (8% vs. 40%, p = 0.044). Group AB plasma use was decreased by 96.6%.

CONCLUSION: Use of Group A for emergency release plasma resulted in ABO-incompatible transfusions; however, this had little effect on clinical outcomes. Blood banks reticent to adopt massive transfusion protocols owing to supply concerns may safely use plasma Group A, expanding the pool of emergency release plasma donors.

LEVEL OF EVIDENCE: Therapeutic study, level IV; prognostic study, level III.

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Ketamine & cardiovascular stability

I ‘jumped ship’ from etomidate to ketamine for rapid sequence intubation (RSI) in sick patients about seven years ago. Good thing too, since I later moved to Australia where we don’t have etomidate. I’ve been one of the aggressive influences behind my prehospital service’s switch to ketamine as the standard induction agent for prehospital RSI. It’s no secret that I think propofol has no place in RSI in the critically ill.
I love ketamine for its haemodynamic stability compared with other induction agents. In fact, I very rarely see a drop in blood pressure when I use it for RSI even in significantly shocked patients. One should however try to remain open to evidence that disconfirms ones biases, lest we allow science to be replaced by religion. I therefore was interested to read a report of two cases of cardiac arrest following the administration of ketamine for rapid sequence intubation (RSI)(1).

ketamine-arrest.003

The first case was a 25 year old with septic shock due to an intestinal perforation, with a respiratory rate of 30 ‘labored’ breaths per minute and hypoxaemia prior to intubation with 2mg/kg ketamine who became bradycardic and then had a 10-15 minute PEA arrest after ketamine administration (but prior to intubation). Pre-arrest oxygen saturation and pre-induction blood gases are not reported.
The second case was an 11 year old with septic shock and pneumonia, hypoxaemia, and a severe metabolic acidosis. She arrested with bradycardia then a brief period of asystole one minute after receiving 2.4 mg/kg ketamine with rocuronium for intubation.
Was the ketamine responsible for the arrests? Ketamine usually exhibits a stimulatory effect on the cardiovascular system, through effects which are incompletely understood but include a centrally mediated sympathetic response and probable inhibition of norepinephrine (noradrenaline) reuptake. However ketamine can have a direct depressant effect on cardiac output which is usually overridden by the sympathetic stimulation. In critically ill severely stressed patients the depressant effect may predominate. In a study on 12 critically ill surgical patients, haemodynamic indices were measured using pulmonary artery catheters within 5 minutes of ketamine administration (at a mean of 70 mg)(2). Six patients demonstrated decreases in ventricular contractility, and four had decreases in cardiac output. Mean arterial blood pressure decreased in four patients. The authors commented:


The patients..were septic, hypovolemic, or cirrhotic, and had severe stress preoperatively. It is possible that in these ill patients adrenocortical and catechol stores had been depleted prior to ketamine administration. Alternatively, in the setting of prolonged preoperative stress, there may be resistance to further sympathetic and/or adrenocotical stimulation by ketamine. In either case, preoperative stress may blunt the usual physiologic responses to ketamine, setting the stage for possible adverse effects.

The negative cardiovascular effects of ketamine may also be precipitated by larger doses or repeated doses of ketamine(3).
While this small case series of cardiac arrest following ketamine administration is interesting, we should bear in mind the other possible precipitants of arrest in these patients, which are not all discussed by the authors:
i) Both patients were hypoxaemic prior to induction and their peri-intubation oxygen saturations are not reported. Arrests following bradycardia at the time of induction in the critically ill are frequently related to hypoxaemia.
ii) The second patient had a severe metabolic acidosis and the first – an abdominal sepsis patient with a labored respiratory rate of 30 – very probably did too. A failure to match a patient’s compensatory respiratory alkalosis with hyperventilation after anaesthesia is known to precipitate arrest in acidaemic patients.
iii) Finally, if the ketamine was responsible for the arrests, one should consider that the doses given to these shocked and highly unstable patients were well in excess of what many of us would recommend, and doses in the range of 0.5-1 mg/kg might not have been associated with adverse effects.
The takehome points for me are that this report is a helpful reminder that the cardiovascular stimulation-inhibition balance of ketamine may be altered by severe critical illness, and that doses of any induction agent should be significantly reduced in the critically ill patient. In no way does this convince me that I should discard ketamine as my preferred choice for RSI in such patients.
1. Cardiac Arrest Following Ketamine Administration for Rapid Sequence Intubation
J Intensive Care Med. 2012 May 29. [Epub ahead of print]
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Given their relative hemodynamic stability, ketamine and etomidate are commonly chosen anesthetic agents for sedation during the endotracheal intubation of critically ill patients. As the use of etomidate has come into question particularly in patients with sepsis, due to its effect of adrenal suppression, there has been a shift in practice with more reliance on ketamine. However, as ketamine relies on a secondary sympathomimetic effect for its cardiovascular stability, cardiovascular and hemodynamic compromise may occur in patients who are catecholamine depleted. We present 2 critically ill patients who experienced cardiac arrest following the administration of ketamine for rapid sequence intubation (RSI). The literature regarding the use of etomidate and ketamine for RSI in critically ill patients is reviewed and options for sedation during endotracheal intubation in this population are discussed.

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2. Cardiovascular effects of anesthetic induction with ketamine
Anesth Analg. 1980 May;59(5):355-8
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Anesthetic induction with ketamine has been reported to maintain or improve cardiovascular performance in severely ill patients. Using invasive cardiovascular monitoring, we studied physiologic responses to a single dose of ketamine in 12 critically ill patients. Six patient demonstrated decreases in ventricular contractility, and four had decreases in cardiac output. Mean arterial blood pressure decreased in four patients. Pulmonary venous admixture increased in four of six patients, while oxygen consumption decreased in eight of 11 patients. Thus, a single dose of ketamine produced decreases in cardiac and pulmonary performance and in peripheral oxygen transport in this group of patients. It is proposed that in severely ill patients, preoperative stress may alter the usual physiologic responses to ketamine administration, and adverse effects may predominate. Ketamine, therefore, should be used with caution for induction of anesthesia in critically ill and in acutely traumatized patients until additional studies and further information on cardiovascular responses to ketamine are available.

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3. A comparison of some cardiorespiratory effects of althesin and ketamine when used for induction of anaesthesia in patients with cardiac disease
Br J Anaesth. 1976 Nov;48(11):1071-81
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Cardiorespiratory effects of ketamine and Althesin were measured in two groups of premedicated patients with cardiac disease. The drugs were given in clinically equivalent doses with a second dose administered about 10 min after induction. The first dose of ketamine caused a marked increase in systemic and pulmonary arterial pressure, heart rate, and central venous and wedge pressures and cardiac index. The first dose of Althesin caused a decrease in systemic arterial pressure, central venous pressure, cardiac index and heart work, but little change in heart rate. The second dose of induction agent was administered before the cardiorespiratory effects of the initial dose had resolved. The second dose of Althesin caused changes similar to those following the first dose, but less marked. The changes following the second dose of ketamine were opposite to those following the first dose.

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New Sepsis Guidelines

pumpsThe latest update of the Surviving Sepsis Campaign Guidelines has been released.
There’s too much interesting stuff to easily summarise, but luckily the full text article is available at the link below.
Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012
Crit Care Med 2013 Feb;41(2):580-637 FREE FULL TEXT