Category Archives: Acute Med

Acute care of the medically sick adult

Acute Med, All Updates, ICU, PHARM, Resus

End-Tidal CO2 as a Predictor of Cardiac Arrest Survival

Leave a comment



In one of largest studies to date of prehospital capnography in cardiac arrest, an initial EtCO2 >10 mmHg (1.3 kPa) was associated with an almost five-fold higher rate of return of spontaneous circulation (ROSC). In addition, a decrease in the EtCO2 during resuscitative events of >25% was associated with a significant increase in mortality, independent of other variables known to affect outcome.

The authors conclude: “EtCO2 values should be included as important variables in protocols to terminate or continue resuscitation in the prehospital setting“.


OBJECTIVE: The objective of this study was to evaluate initial end-tidal CO2 (EtCO2) as a predictor of survival in out-of-hospital cardiac arrest.

METHODS: This was a retrospective study of all adult, non-traumatic, out-of-hospital, cardiac arrests during 2006 and 2007 in Los Angeles, California. The primary outcome variable was attaining return of spontaneous circulation (ROSC) in the field. All demographic information was reviewed and logistic regression analysis was performed to determine which variables of the cardiac arrest were significantly associated with ROSC.

RESULTS: There were 3,121 cardiac arrests included in the study, of which 1,689 (54.4%) were witnessed, and 516 (16.9%) were primary ventricular fibrillation (VF). The mean initial EtCO2 was 18.7 (95%CI = 18.2-19.3) for all patients. Return of spontaneous circulation was achieved in 695 patients (22.4%) for which the mean initial EtCO2 was 27.6 (95%CI = 26.3-29.0). For patients who failed to achieve ROSC, the mean EtCO2 was 16.0 (95%CI = 15.5-16.5). The following variables were significantly associated with achieving ROSC: witnessed arrest (OR = 1.51; 95%CI = 1.07-2.12); initial EtCO2 >10 (OR = 4.79; 95%CI = 3.10-4.42); and EtCO2 dropping <25% during the resuscitation (OR = 2.82; 95%CI = 2.01-3.97).The combination of male gender, lack of bystander cardiopulmonary resuscitation, unwitnessed collapse, non-vfib arrest, initial EtCO2 ≤10 and EtCO2 falling > 25% was 97% predictive of failure to achieve ROSC.

CONCLUSIONS: An initial EtCO2 >10 and the absence of a falling EtCO2 >25% from baseline were significantly associated with achieving ROSC in out-of-hospital cardiac arrest. These additional variables should be incorporated in termination of resuscitation algorithms in the prehospital setting.

End-Tidal CO2 as a Predictor of Survival in Out-of-Hospital Cardiac Arres
Prehosp Disaster Med. 2011 Jun;26(3):148-50

Acute Med, All Updates, PHARM, Resus

Nebulised naloxone

Leave a comment

This appears to be a useful option when iv access is difficult and the patient is relatively stable.
The protocol specified nebulisation of 2 mg of naloxone with 3 mL of normal saline as empiric treatment for suspected opioid overdose or undifferentiated depressed respirations as long as the patient had some spontaneous respiratory effort, no apnoea, and no severe cardiorespiratory compromise.


BACKGROUND: Emergency medical services (EMS) traditionally administer naloxone using a needle. Needleless naloxone may be easier when intravenous (IV) access is difficult and may decrease occupational blood-borne exposure in this high-risk population. Several studies have examined intranasal naloxone, but nebulized naloxone as an alternative needleless route has not been examined in the prehospital setting.

OBJECTIVE: We sought to determine whether nebulized naloxone can be used safely and effectively by prehospital providers for patients with suspected opioid overdose.

METHODS: We performed a retrospective analysis of all consecutive cases administered nebulized naloxone from January 1 to June 30, 2010, by the Chicago Fire Department. All clinical data were entered in real time into a structured EMS database and data abstraction was performed in a systematic manner. Included were cases of suspected opioid overdose, altered mental status, and respiratory depression; excluded were cases where nebulized naloxone was given for opioid-triggered asthma and cases with incomplete outcome data. The primary outcome was patient response to nebulized naloxone. Secondary outcomes included need for rescue naloxone (IV or intramuscular), need for assisted ventilation, and adverse antidote events. Kappa interrater reliability was calculated and study data were analyzed using descriptive statistics.

RESULTS: Out of 129 cases, 105 met the inclusion criteria. Of these, 23 (22%) had complete response, 62 (59%) had partial response, and 20 (19%) had no response. Eleven cases (10%) received rescue naloxone, no case required assisted ventilation, and no adverse events occurred. The kappa score was 0.993.

CONCLUSION: Nebulized naloxone is a safe and effective needleless alternative for prehospital treatment of suspected opioid overdose in patients with spontaneous respirations.

Can nebulized naloxone be used safely and effectively by emergency medical services for suspected opioid overdose?
Prehosp Emerg Care, 2012 vol. 16 (2):289-292

Acute Med, All Updates, ICU, Resus

Nitrate bolus in acute heart failure

Leave a comment

Despite intravenous nitrate boluses being used in original studies demonstrating benefit in acute heart failure1,2, I regularly meet reluctance from both physicians and nurses in the emergency department to give them.
Their resistance seems to be based on a concern for inducing hypotension, and they prefer to ‘titrate up’ an infusion.
iv nitrate options include nitroglycerin (GTN), and isosorbide dinitrate (ISDN). Studies have used ISDN 4mg every 4 mins, ISDN 3mg every 5 mins, and GTN 2mg every 3 mins3.
There are a number of reasons to avoid starting with a low rate infusion in a sick heart failure patient.
Matthew Reed highlighted cannula size as an important factor4:


If a GTN infusion is commenced at a rate of 1 ml/h, a critically unwell patient with a large cannula—for example, a grey cannula (16G) — will have to wait over 6 min for the drug to enter the body. This compares with 1.5 min for a pink cannula (20G) at the same infusion rate. If a large-diameter cannula is chosen for these patients, then a fast initial infusion rate should also be chosen to ensure that the GTN begins to act quickly.

Alistair Steel subsequently pointed out further reasons to avoid slow infusions5:


(1) mechanical slack within an infusion device may mean an infusion set at 1 ml/h will take many minutes for the driver to contact and advance the syringe plunger. For this reason, infusions should be purged before patient connection.

(2) the pharmacokinetics of the drug should be considered. At low infusion rates it will take significant time for a steady state to be achieved (a drug such as GTN, with a half-life of 2 min, would require 10 min to achieve steady state). For clinical effects to be seen quickly, a bolus should be given before commencing infusions.

(3) the use of 1 ml/h infusions (8 µg/min using a 0.5% solution) may be excessively cautious – the British National Formulary recommends a therapeutic dose range from 10 to 200 µg/min. Furthermore, there is emerging evidence that, when used for decompensated heart failure, higher doses of GTN are associated with more favourable outcomes.

(4) at low infusion rates any obstruction in the intravenous system will take a proportionally longer time to become apparent, as it will take longer for the pressure to build up and trigger the syringe pump’s high pressure alarm..

Now a recent study confirms such a regimen can be used safely in the elderly. ISDN 3mg bolus treatment was not associated with higher rates of hypotension in the elderly population treated for heart failure in the emergency department. Despite a small study and a retrospective design, this lends support to the practice of iv bolus nitrate therapy for acute heart failure, even in the elderly.
1. Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema
Lancet. 1998 Feb 7;351(9100):389-93
2. High-doses intravenous isosorbide dinitrate is safer and better than Bi-PAP ventilation combined with conventional treatment for severe pulmonary edema
J Am Coll Cardiol. 2000 Sep;36(3):832-7 Free Full Text
3. Managing acute pulmonary oedema with high or standard dose nitrate
Emerg Med J. 2009 May;26(5):357-8
4. Administering a glyceryl trinitrate infusion: big is not always best
Emerg Med J 2007;24:423-424
5. Administering a glyceryl trinitrate infusion: faster is better than slower
Emerg Med J. 2008 Jan;25(1):60
6. Isosorbide dinitrate bolus for heart failure in elderly emergency patients: a retrospective study
Eur J Emerg Med. 2011 Oct;18(5):272-5

Acute Med, All Updates, ICU, PHARM, Resus

In CPR depth is good, but how deep to compress?

Leave a comment

Some defibrillators have accelerometers capable of measuring chest compression depth during CPR. This allowed a study correlating compression depth with survival in out of hospital cardiac arrest.
More than half of patients received less than the 2005 recommended chest compression depth of 38–51 mm and >90% received less than the 2010 recommended depth of >50 mm. There was an inverse relationship between rate and depth, ie. rescuers had a tendency to ‘push hard, push slow’ or ‘push soft, push fast’.
The authors state:
We found an association between adequate compression depth and good outcomes but could not demonstrate that the 2010 recommendations are better than those from 2005. Although we believe that compression depth is an important component of CPR and should be measured routinely during cardiac arrest resuscitation, we believe that the optimal depth is currently unknown.


BACKGROUND: The 2010 international guidelines for cardiopulmonary resuscitation recently recommended an increase in the minimum compression depth from 38 to 50 mm, although there are limited human data to support this. We sought to study patterns of cardiopulmonary resuscitation compression depth and their associations with patient outcomes in out-of-hospital cardiac arrest cases treated by the 2005 guideline standards.

DESIGN: Prospective cohort.

SETTING: Seven U.S. and Canadian urban regions.

PATIENTS: We studied emergency medical services treated out-of-hospital cardiac arrest patients from the Resuscitation Outcomes Consortium Epistry-Cardiac Arrest for whom electronic cardiopulmonary resuscitation compression depth data were available, from May 2006 to June 2009.

MEASUREMENTS: We calculated anterior chest wall depression in millimeters and the period of active cardiopulmonary resuscitation (chest compression fraction) for each minute of cardiopulmonary resuscitation. We controlled for covariates including compression rate and calculated adjusted odds ratios for any return of spontaneous circulation, 1-day survival, and hospital discharge.

MAIN RESULTS: We included 1029 adult patients from seven U.S. and Canadian cities with the following characteristics: Mean age 68 yrs; male 62%; bystander witnessed 40%; bystander cardiopulmonary resuscitation 37%; initial rhythms: Ventricular fibrillation/ventricular tachycardia 24%, pulseless electrical activity 16%, asystole 48%, other nonshockable 12%; outcomes: Return of spontaneous circulation 26%, 1-day survival 18%, discharge 5%. For all patients, median compression rate was 106 per minute, median compression fraction 0.65, and median compression depth 37.3 mm with 52.8% of cases having depth <38 mm and 91.6% having depth <50 mm. We found an inverse association between depth and compression rate ( p < .001). Adjusted odds ratios for all depth measures (mean values, categories, and range) showed strong trends toward better outcomes with increased depth for all three survival measures.
CONCLUSIONS: We found suboptimal compression depth in half of patients by 2005 guideline standards and almost all by 2010 standards as well as an inverse association between compression depth and rate. We found a strong association between survival outcomes and increased compression depth but no clear evidence to support or refute the 2010 recommendations of >50 mm. Although compression depth is an important component of cardiopulmonary resuscitation and should be measured routinely, the most effective depth is currently unknown.

What is the role of chest compression depth during out-of-hospital cardiac arrest resuscitation?
Crit Care Med. 2012 Apr;40(4):1192-8

Acute Med, All Updates, ICU, Resus, Trauma

Red cell transfusion guidelines

Leave a comment

The AABB (formerly the American Association of Blood Banks has issued guidelines on red blood cell transfusion1, providing some number-based targets which may be helpful for some practitioners or organisations. Editorialist and heavyweight intensivist Jean-Louis Vincent argues for a more individual patient-based assessment2, and highlights some of the weaknesses of existing studies, in particular the often quoted but now fairly old TRICC study3 which suffered from poor recruitment and the possible lack of applicability to modern practice now that leucodepleted products are used.
Prof Vincent states:
“Transfusion decisions need to consider individual patient characteristics, including age and the presence of CAD, to estimate a specific patient’s likelihood of benefit from transfusion. The decision to transfuse is too complex and important to be guided by a single number.”


Description: Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American Association of Blood Banks) developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children.

Methods: These guidelines are based on a systematic review of the literature on randomized clinical trials evaluating transfusion thresholds. We performed a literature search from 1950 to February 2011 with no language restrictions. We examined the proportion of patients who received any RBC transfusion and the number of RBC units transfused to describe the effect of restrictive transfusion strategies on RBC use. To determine the clinical consequences of restrictive transfusion strategies, we examined overall mortality, nonfatal myocardial infarction, cardiac events, pulmonary edema, stroke, thromboembolism, renal failure, infection, hemorrhage, mental confusion, functional recovery, and length of hospital stay.

Recommendation 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence).

Recommendation 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence).

Recommendation 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence).

Recommendation 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence).

1. Red Blood Cell Transfusion: A Clinical Practice Guideline From the AABB
Ann Intern Med. 2012 Mar 26. [Epub ahead of print] Full Text
2. Indications for Blood Transfusions: Too Complex to Base on a Single Number?
Ann Intern Med. 2012 Mar 26. [Epub ahead of print] Full Text
3. A Multicenter, Randomized, Controlled Clinical Trial of Transfusion Requirements in Critical Care
N Engl J Med 1999; 340:409-417 Full Text

Acute Med, All Updates, Guidelines, ICU, PHARM, Resus, Trauma, Ultrasound

International recommendations for lung ultrasound

Leave a comment

A multidisciplinary panel of 28 experts from eight countries reviewed the literature and came up with consensus guidelines in point-of-care lung ultrasound. There were some big names involved – all the big players in emergency/critical care ultrasound from around the World. Conspicuously absent were Matt and Mike from the Emergency Ultrasound Podcast, but maybe there was a maximum awesomeness limit or something.

Here are some snippets, taken out of context and without the grade of recommendation attached. Try to get hold of the original if you can, which might not be easy. I never understand it when ‘international recommendations’ are published as subscription-only articles. Either they want people to follow them or not. Oh well – here are some of their recommendations:
Pneumothorax

  • The sonographic signs of pneumothorax include the following: Presence of lung point(s); Absence of lung sliding; Absence of B-lines; Absence of lung pulse
  • The lung pulse refers to the subtle rhythmic movement of the visceral upon the parietal pleura with cardiac oscillations and is a rule-out sign for pneumothorax
  • In the supine patient, the sonographic technique consists of exploration of the least gravitationally dependent areas progressing more laterally.
  • Bedside lung ultrasound is a useful tool to differentiate between small and large pneumothorax, using detection of the lung point.

Interstitial syndrome

  • B-lines are defined as discrete laser-like vertical hyperechoic reverberation artifacts that arise from the pleural line (previously described as ‘‘comet tails’’), extend to the bottom of the screen without fading, and move synchronously with lung sliding.
  • The presence of multiple diffuse bilateral B-lines indicates interstitial syndrome. Causes of interstitial syndrome include the following conditions: Pulmonary edema of various causes; Interstitial pneumonia or pneumonitis; Diffuse parenchymal lung disease (pulmonary fibrosis)

Lung consolidation

  • The sonographic sign of lung consolidation is a subpleural echo-poor region or one with tissue-like echotexture.
  • Lung ultrasound is a clinically useful tool to rule in pneumonia; however, lung ultrasound does not rule out consolidations that do not reach the pleura.
  • In mechanically ventilated patients lung ultrasound should be considered as it is more accurate than portable chest radiography in the detection of consolidation.

Pleural effusion

  • Both of the following signs are present in almost all free effusions: A space (usually anechoic) between the parietal and visceral pleura; Respiratory movement of the lung within the effusion (‘‘sinusoid sign’’)
  • In opacities identified by chest radiography, lung ultrasound should be used because it is more accurate than chest radiography in distinguishing between effusion and consolidation.
  • Visualization of internal echoes, either of mobile particles or septa, is highly suggestive of exudate or hemothorax


BACKGROUND: The purpose of this study is to provide evidence-based and expert consensus recommendations for lung ultrasound with focus on emergency and critical care settings.

METHODS: A multidisciplinary panel of 28 experts from eight countries was involved. Literature was reviewed from January 1966 to June 2011. Consensus members searched multiple databases including Pubmed, Medline, OVID, Embase, and others. The process used to develop these evidence-based recommendations involved two phases: determining the level of quality of evidence and developing the recommendation. The quality of evidence is assessed by the grading of recommendation, assessment, development, and evaluation (GRADE) method. However, the GRADE system does not enforce a specific method on how the panel should reach decisions during the consensus process. Our methodology committee decided to utilize the RAND appropriateness method for panel judgment and decisions/consensus.

RESULTS: Seventy-three proposed statements were examined and discussed in three conferences held in Bologna, Pisa, and Rome. Each conference included two rounds of face-to-face modified Delphi technique. Anonymous panel voting followed each round. The panel did not reach an agreement and therefore did not adopt any recommendations for six statements. Weak/conditional recommendations were made for 2 statements, and strong recommendations were made for the remaining 65 statements. The statements were then recategorized and grouped to their current format. Internal and external peer-review processes took place before submission of the recommendations. Updates will occur at least every 4 years or whenever significant major changes in evidence appear.

CONCLUSIONS: This document reflects the overall results of the first consensus conference on “point-of-care” lung ultrasound. Statements were discussed and elaborated by experts who published the vast majority of papers on clinical use of lung ultrasound in the last 20 years. Recommendations were produced to guide implementation, development, and standardization of lung ultrasound in all relevant settings.

International evidence-based recommendations for point-of-care lung ultrasound
Intensive Care Med. 2012 Apr;38(4):577-91

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

Clotbusting wisdom on tap – your questions answered

Leave a comment

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?

Leave a comment

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

Acute Med, All Updates, Guidelines, PHARM, Resus

Epinephrine in cardiac arrest reanalysed

Leave a comment

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

Leave a comment

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