Yearly Archives: 2012

All Updates, ICU, Resus

Phentolamine for neurogenic pulmonary oedema

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A single case report might not be practice changing, but it’s helpful to know about this option:
A patient with acute intracerebral haemorrhage developed hyoxaemia due to neurogenic pulmonary oedema, accompanied by a labile blood pressure and elevated catecholamine levels.
Nicardipine and other antihypertensive agents including metoprolol, hydralazine, and labetalol were tried without benefit, and the patient continued to deteriorate.
Phentolamine was tried. The introduction, withdrawal, and reintroduction of phentolamine and the clinical status of the patient is described convincingly:


a phentolamine infusion was started at 0.17 mg/min and titrated for BP control. Over 6 h, the FIO2 requirements dropped precipitously, gas exchange improved, and the chest radiograph showed improvement of pulmonary edema. When the hospital supply of phentolamine was exhausted, the clinical status deteriorated rapidly. Within just 15 h of the discontinuation of phentolamine, the PaO2 fell from 166 mm Hg to 66 mm Hg, and FIO2 requirements rose from 60% to 100%. When the phentolamine supply was replenished and the infusion restarted, the same rapid improvement was observed and BP stabilized.

Phentolamine is a potent competitive antagonist at both alpha 1 and alpha 2 receptors . Phentolamine causes a reduction in peripheral resistance through blockade of alpha 1 receptors and possibly alpha 2 receptors on vascular smooth muscle.


Abstract
Neurogenic pulmonary edema (NPE) is a clinical syndrome characterized by the acute onset of pulmonary edema following a significant CNS insult. The cause is believed to be a surge of catecholamines that results in cardiopulmonary dysfunction. Although there are myriad case reports describing CNS events that are associated with this syndrome, few studies have identified specific treatment modalities. We present a case of NPE caused by an intracranial hemorrhage from a ruptured arteriovenous malformation. We uniquely document a rise and fall of serum catecholamine levels correlating with disease activity and a dramatic clinical response to IV phentolamine.

Neurogenic Pulmonary Edema: Successful Treatment With IV Phentolamine
Chest March 2012 vol. 141 no. 3 793-795

Acute Med, All Updates, Guidelines, ICU, Kids, Resus

Clotbusting wisdom on tap – your questions answered

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The prevention and management of venous thromboembolic disease is a huge topic, which generates questions for emergency, critical care, and acute physicians during many shifts:

  • How long should someone requiring cardioversion for atrial fibrillation be anticoagulated for?
  • How should I provide thromboprophylaxis for this intubated patient?
  • This patient with submassive pulmonary embolism isn’t hypotensive yet. Can I thrombolyse them? Can I?
  • There’s a large superficial vein thrombosis in that limb – is anticoagulation indicated?
  • This asymptomatic patient on warfarin has an INR of 9.0 – should I reverse them?
  • Do I need to add Vitamin K if I’ve reversed warfarin with prothrombin complex concentrate?

The answers to these – and many, many more – questions are provided in one of the most comprehensive guidelines I’ve ever come across. I can see myself clicking on the link below in future when on duty in the ED.
Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines
Chest. 2012 Feb;141(2 Suppl) Full Text

Acute Med, All Updates, ICU, Resus

Dobutamine for severe heart failure – more harm than good?

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A systematic review and meta-analysis of randomised controlled trials showed dobutamine is not associated with improved mortality in heart failure patients and in the case of severe heart failure there is some suggestion of increased mortality, although this did not reach statistical significance.
The authors do point out that the quality of the reports of the trials reviewed was suboptimal. However, they state:
It should be noted that the results of this study are in accord with large observational studies that have also suggested harm associated with use of dobutamine in patients with severe heart failure. Taken together, this evidence should cause clinicians to reconsider their use of dobutamine in patients with heart failure, particularly those most at risk of the adverse effects, those with underlying ischaemic heart disease.

PURPOSE: Dobutamine is recommended for patients with severe heart failure; however uncertainty exists as to its effect on mortality. This study aims to critically review the literature to evaluate whether dobutamine, compared with placebo or standard care, is associated with lower mortality and a range of secondary outcomes, in patients with severe heart failure.
METHODS: A systematic review and meta-analysis of randomised controlled trials was performed. PubMed, EMBASE, the Cochrane Central Trials Registry, the metaRegister of Controlled Trials and bibliographies of retrieved articles were searched. Randomised trials comparing dobutamine with placebo or standard care, in human, adult patients with severe heart failure, were included if they reported at least one outcome of interest. Data regarding trial validity, methodological processes and clinical outcomes were extracted, and a meta-analysis was performed.
RESULTS: Fourteen studies, with 673 participants, met the inclusion criteria and were included; 13 studies reported mortality. There was minimal heterogeneity (I (2) = 4.5%). The estimate of the odds ratio for mortality for patients with severe heart failure treated with dobutamine compared with standard care or placebo was 1.47 (95% confidence interval 0.98-2.21, p = 0.06).
CONCLUSIONS: This meta-analysis showed that dobutamine is not associated with improved mortality in patients with heart failure, and there is a suggestion of increased mortality associated with its use, although this did not reach the conventional level of statistical significance. Further research to define the role of dobutamine in treatment of severe heart failure should be a priority.

Dobutamine for patients with severe heart failure- a systematic review and meta-analysis of randomised controlled trials
Intensive Care Med. 2012 Mar;38(3):359-67

All Updates, Guidelines, ICU, Resus

Colloid volume therapy for critically ill patients

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The European Society of Intensive Care Medicine has produced a consensus statement on colloid volume therapy for critically ill patients, published in this month’s Intensive Care Medicine.
Curiously, the full text document is not yet availablle on ESICM’s website, but I found this presentation summarising the work by one the authors (Richard Beale):


PURPOSE: Colloids are administered to more patients than crystalloids, although recent evidence suggests that colloids may possibly be harmful in some patients. The European Society of Intensive Care Medicine therefore assembled a task force to compile consensus recommendations based on the current best evidence for the safety and efficacy of the currently most frequently used colloids-hydroxyethyl starches (HES), gelatins and human albumin.

METHODS: Meta-analyses, systematic reviews and clinical studies of colloid use were evaluated for the treatment of volume depletion in mixed intensive care unit (ICU), cardiac surgery, head injury, sepsis and organ donor patients. Clinical endpoints included mortality, kidney function and bleeding. The relevance of concentration and dosage was also assessed. Publications from 1960 until May 2011 were included. The quality of available evidence and strength of recommendations were based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

RECOMMENDATIONS AND CONCLUSIONS: We recommend not to use HES with molecular weight ≥200 kDa and/or degree of substitution >0.4 in patients with severe sepsis or risk of acute kidney injury and suggest not to use 6% HES 130/0.4 or gelatin in these populations. We recommend not to use colloids in patients with head injury and not to administer gelatins and HES in organ donors. We suggest not to use hyperoncotic solutions for fluid resuscitation. We conclude and recommend that any new colloid should be introduced into clinical practice only after its patient-important safety parameters are established.

Consensus statement of the ESICM task force on colloid volume therapy in critically ill patients
Intensive Care Med. 2012 Mar;38(3):368-83
Update September 2012:
An RCT showed patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer’s acetate. Read more about the trial here
Hydroxyethyl Starch 130/0.42 versus Ringer’s Acetate in Severe Sepsis
N Engl J Med. 2012 Jul 12;367(2):124-34
Australian intensivist John Myburgh gives a great summary of Fluid Therapy in critical care here

All Updates, PHARM, Trauma

Body temperature in anaesthetised HEMS patients

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This study raises an important issue – how do we keep patients with major trauma warm on the way to hospital? The authors from HEMS London identified mean temperatures in hospital of 35°C in patients who had been anaesthetised in the field, although only 38% of their patients had a temperature recorded on admission!
I emailed the author Audun Langhelle for practical information on the thermal protection package they use, who was most helpful in supplying the following information. Clicking on the link will take you to online supplements to the paper describing and illustrating their technique of prehospital rewarming.

Hi Cliff,

Thank you for your request and interest in our paper. Now fully repatriated to Norway, we’re currently using the medium sized UniqueResc warming blanket (Geratherm, Germany) at my base, together with the bubble wrap. In Norway, Garatherm is the only company which has been able to provide us with the necessary paper work showing that their product complies with the rather strict pan European rules and regulations, the EN 13718-1: Requirements for medical devices used in air ambulances in particular.
Working as HEMS doc with LAA 2008-2009, we played with and introduced the policy using Diemme’s (Italy)DM EMG >> http://emj.bmj.com/content/early/2010/10/19/emj.2009.086967/suppl/DC1, but I’m not sure what blanket they currently use.

Kind regards,

Audun

We reviewed this article in one of our Sydney HEMS Clinical Governance Days last year. One of our team presented a critical appraisal and if you’re interested the deadly PowerPoint slides are here:

Body temperature of trauma patients on admission to hospital

View more presentations from nswhems.


Background Hypothermia at hospital admission has been found to independently predict increased mortality in trauma patients.

Objectives To establish if patients anaesthetised in the prehospital phase of care had a higher rate of hypothermia than non-anaesthetised patients on admission to hospital.

Methods Retrospective review of admission body temperature in 1292 consecutive prehospital trauma patients attended by a physician-led prehospital trauma service admitted to The Royal London Hospital between 1 July 2005 and 31 December 2008.

Results 38% had a temperature recorded on admission. There was a significant difference in body temperature between the anaesthetised group (N=207) and the non-anaesthetised group (N=287): mean (SD) 35.0 (2.1) vs 36.2 (1.0)°C, respectively (p <0.001). No significant seasonal body temperature variation was demonstrated.
Conclusion This study confirmed that patients anaesthetised in the prehospital phase of care had a significantly lower admission body temperature. This has led to a change in the author’s prehospital practice. Anaesthetised patients are now actively surface heated and have whole body insulation to prevent further heat loss in an attempt to conserve body temperature and improve outcome. This is an example of best in-hospital anaesthetic practice being carried out in the prehospital phase.

Body temperature of trauma patients on admission to hospital: a comparison of anaesthetised and non-anaesthetised patients
Emerg Med J. 2012 Mar;29(3):239-42
Full text link

Acute Med, All Updates, Guidelines, PHARM, Resus

Epinephrine in cardiac arrest reanalysed

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A post hoc reanalysis was performed on a 2009 JAMA paper comparing patients randomised to receive or not receive prehospital drugs and iv access for cardiac arrest.
This was done to evaulate the effect of adrenaline/epinephrine. The reason for the reanalysis was that in the original intention-to-treat analysis, some of the following issues may have influenced the results:

  • Some patients randomised to adrenaline never received it as they had ROSC before the drug could be given, thus yielding a selection bias with the most easily resuscitated patients in the post hoc no-adrenaline group
  • At least 1 of 5 patients randomised to receive IV access and drugs did not receive adrenaline as it was regarded futile or it was impossible to gain intravenous access
  • 1 of 10 patients randomised to not receive drugs received adrenaline after they had regained spontaneous circulation for > 5 min.

The purpose of this post hoc analysis on the RCT data was to compare outcomes for patients actually receiving adrenaline to those not receiving adrenaline.
The actual use of adrenaline was associated with increased short-term survival, but with 48% less survival to hospital discharge. The improved survival to hospital admission is consistent with the results of a recent Australia study, and the negative association with longer term survival is similar to a multivariate analysis of observational Swedish registry data where patients receiving adrenaline were 57% less likely to be alive after one month.
Yet more evidence that we haven’t found any drugs proven to improve survival in cardiac arrest. At least not until the human studies on sodium nitroprusside come out?
I bet some of you are still going to be giving the epi exactly every four minutes though.
**Update: see Prehospital Epinephrine Use and Survival Among Patients With Out-of-Hospital Cardiac Arrest – more prospective data from Japan, this time showing epinephrine improves prehospital ROSC, but decreases chance of survival and good functional outcomes 1 month after the event.**


PURPOSE OF THE STUDY: IV line insertion and drugs did not affect long-term survival in an out-of-hospital cardiac arrest (OHCA) randomized clinical trial (RCT). In a previous large registry study adrenaline was negatively associated with survival from OHCA. The present post hoc analysis on the RCT data compares outcomes for patients actually receiving adrenaline to those not receiving adrenaline.

MATERIALS AND METHODS: : Patients from a RCT performed May 2003 to April 2008 were included. Three patients from the original intention-to-treat analysis were excluded due to insufficient documentation of adrenaline administration. Quality of cardiopulmonary resuscitation (CPR) and clinical outcomes were compared.

RESULTS: Clinical characteristics were similar and CPR quality comparable and within guideline recommendations for 367 patients receiving adrenaline and 481 patients not receiving adrenaline. Odds ratio (OR) for being admitted to hospital, being discharged from hospital and surviving with favourable neurological outcome for the adrenaline vs. no-adrenaline group was 2.5 (CI 1.9, 3.4), 0.5 (CI 0.3, 0.8) and 0.4 (CI 0.2, 0.7), respectively. Ventricular fibrillation, response interval, witnessed arrest, gender, age and endotracheal intubation were confounders in multivariate logistic regression analysis. OR for survival for adrenaline vs. no-adrenaline adjusted for confounders was 0.52 (95% CI: 0.29, 0.92).

CONCLUSION: Receiving adrenaline was associated with improved short-term survival, but decreased survival to hospital discharge and survival with favourable neurological outcome after OHCA. This post hoc survival analysis is in contrast to the previous intention-to-treat analysis of the same data, but agrees with previous non-randomized registry data. This shows limitations of non-randomized or non-intention-to-treat analyses.

Outcome when adrenaline (epinephrine) was actually given vs. not given – post hoc analysis of a randomized clinical trial
Resuscitation. 2012 Mar;83(3):327-32

Acute Med, All Updates, PHARM

Prehospital IM midazolam for seizures

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Intramuscular midazolam is at least as safe and effective as intravenous lorazepam for the prehospital management of status epilepticus. In his blog EM Literature of Note, Dr Ryan Radecki looks forward to a similar trial comparing nasal midazolam, which would reduce the risk from injections. Read his full critique here. Buccal midazolam 0.5 mg/kg is of course also an option, as described in the Advanced Paediatric Life Support manual:
If using the buccal route, draw up the higher dose (0.5mg) of the IV preparation using a needle (to avoid any fragments of glass from the ampoule) and after removing the needle, inject the drug into the buccal area between the lower bottom lip and the gum margin at the side of the mouth. Buccal midazolam is twice as effective as rectal diazepam, but both drugs produce the same level and degree of respiratory depression.


BACKGROUND: Early termination of prolonged seizures with intravenous administration of benzodiazepines improves outcomes. For faster and more reliable administration, paramedics increasingly use an intramuscular route.

METHODS: This double-blind, randomized, noninferiority trial compared the efficacy of intramuscular midazolam with that of intravenous lorazepam for children and adults in status epilepticus treated by paramedics. Subjects whose convulsions had persisted for more than 5 minutes and who were still convulsing after paramedics arrived were given the study medication by either intramuscular autoinjector or intravenous infusion. The primary outcome was absence of seizures at the time of arrival in the emergency department without the need for rescue therapy. Secondary outcomes included endotracheal intubation, recurrent seizures, and timing of treatment relative to the cessation of convulsive seizures. This trial tested the hypothesis that intramuscular midazolam was noninferior to intravenous lorazepam by a margin of 10 percentage points.

RESULTS: At the time of arrival in the emergency department, seizures were absent without rescue therapy in 329 of 448 subjects (73.4%) in the intramuscular-midazolam group and in 282 of 445 (63.4%) in the intravenous-lorazepam group (absolute difference, 10 percentage points; 95% confidence interval, 4.0 to 16.1; P<0.001 for both noninferiority and superiority). The two treatment groups were similar with respect to need for endotracheal intubation (14.1% of subjects with intramuscular midazolam and 14.4% with intravenous lorazepam) and recurrence of seizures (11.4% and 10.6%, respectively). Among subjects whose seizures ceased before arrival in the emergency department, the median times to active treatment were 1.2 minutes in the intramuscular-midazolam group and 4.8 minutes in the intravenous-lorazepam group, with corresponding median times from active treatment to cessation of convulsions of 3.3 minutes and 1.6 minutes. Adverse-event rates were similar in the two groups.
CONCLUSIONS: For subjects in status epilepticus, intramuscular midazolam is at least as safe and effective as intravenous lorazepam for prehospital seizure cessation. (Funded by the National Institute of Neurological Disorders and Stroke and others; ClinicalTrials.gov number, ClinicalTrials.gov NCT00809146.).

Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus
N Engl J Med. 2012 Feb 16;366(7):591-600

All Updates, Fascinomata

Mathematical Art of M.C. Escher

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I am stunned by the beauty and brilliance of this video by Spanish filmmaker Cristóbal Vila – Inspirations: A Short Film Celebrating the Mathematical Art of M.C. Escher.
M.C. Escher (1898-1972) was the Dutch artist who explored a wide range of mathematical ideas with his woodcuts, lithographs, and mezzotints.
The cool bloggers at openculture.com write: Although Escher had no formal training in mathematics beyond secondary school, many mathematicians counted themselves as admirers of his work.

 
INSPIRATIONS from Cristóbal Vila on Vimeo.
 
 
 
If you want to well up further with rapturous contemplation of the beauty of mathematics in nature, check out his other video, Nature by Numbers

Nature by Numbers from Cristóbal Vila on Vimeo.

Acute Med, All Updates, PHARM

Enoxaparin beats heparin for PCI

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This is of interest to those of us in retrieval medicine, for logistic reasons: an infusion of heparin can be an unnecessary hassle during transport, especially if a subcutaneous injection prior to retrieval is a satisfactory alternative. This systematic review and meta-analysis shows enoxaparin appears to be superior to unfractionated heparin in reducing mortality and bleeding outcomes during percutaneous coronary intervention. This applies particularly to patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction


OBJECTIVE: To determine the efficacy and safety of enoxaparin compared with unfractionated heparin during percutaneous coronary intervention.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: Medline and Cochrane database of systematic reviews, January 1996 to May 2011.

STUDY SELECTION: Randomised and non-randomised studies comparing enoxaparin with unfractionated heparin during percutaneous coronary intervention and reporting on both mortality (efficacy end point) and major bleeding (safety end point) outcomes.

DATA EXTRACTION: Sample size, characteristics, and outcomes, extracted independently and analysed.

DATA SYNTHESIS: 23 trials representing 30 966 patients were identified, including 10 243 patients (33.1%) undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction, 8750 (28.2%) undergoing secondary percutaneous coronary intervention after fibrinolysis, and 11 973 (38.7%) with non-ST elevation acute coronary syndrome or stable patients scheduled for percutaneous coronary intervention. A total of 13 943 patients (45.0%) received enoxaparin and 17 023 (55.0%) unfractionated heparin. Enoxaparin was associated with significant reductions in death (relative risk 0.66, 95% confidence interval 0.57 to 0.76; P<0.001), the composite of death or myocardial infarction (0.68, 0.57 to 0.81; P<0.001), and complications of myocardial infarction (0.75, 0.6 to 0.85; P<0.001), and a reduction in incidence of major bleeding (0.80, 0.68 to 0.95; P=0.009). In patients who underwent primary percutaneous coronary intervention, the reduction in death (0.52, 0.42 to 0.64; P<0.001) was particularly significant and associated with a reduction in major bleeding (0.72, 0.56 to 0.93; P=0.01).
CONCLUSION: Enoxaparin seems to be superior to unfractionated heparin in reducing mortality and bleeding outcomes during percutaneous coronary intervention and particularly in patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction.

Efficacy and safety of enoxaparin versus unfractionated heparin during percutaneous coronary intervention: systematic review and meta-analysis
BMJ. 2012 Feb 3;344:e553

All Updates

Scandinavian Critical Care

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If you like the kind of updates posted here at Resus.ME, then check out SCANCRIT. This blog on anaesthesia, intensive care and emergency medicine – in-hospital and outside – is run by two friends of mine who undersell themselves with their description as ‘two Scandinavian senior anaesthetic registrars’.
These marauding Viking resuscitators are so much more. Lock up your daughters and go to www.scancrit.com