Phenylephrine vs. Catecholamines and the (rodent) heart

May 20, 2012 by  
Filed under All Updates

Okay, I don’t normally blog about animal studies, but I thought this would be of interest, particularly to readers of my post ‘Why I don’t give vasopressors in sepsis’ which was followed by some interesting debate between friends Scott, Minh, Aaron and Pete. It supports my view that pure alpha-agonists might fix the numbers on the chart, but are not necessarily helpful in terms of cardiac output and potentially organ perfusion, whereas catecholamines might be more fit for purpose in many shock states including septic shock. If I want to push a ‘pressor’, I use dilute epinephrine, as I think the pure alpha agonists (a group to which norepinephrine does NOT belong) have very few clinical indications – the main one in my view being to counteract iatrogenic vasodilation in the operative anaesthesia setting. I hope this sparks vigorous debate – let’s hear the many ways cats are being skinned out there….


Background: Myocardial depression is a frequent event during septic shock and may mimic a cardiogenic shock state with decreased cardiac output. Nevertheless, data are scarce regarding the myocardial effects of vasopressors used to treat hypotension. In this study, the authors compared the effects of three commonly used vasopressors acting on different adrenergic receptors on myocardial function in a rodent model of septic shock, as explored with conductance catheter and positron emission tomography.

Methods: Septic shock was induced in rats by peritonitis. Eighteen hours after septic insult, vasopressors were titrated to increase mean arterial pressure by 20% compared with baseline values.

Results: We observed that peritonitis was associated with arterial hypotension and systolodiastolic dysfunction. Norepinephrine and epinephrine improved mean arterial pressure, cardiac output, and preload recruitable stroke work, a load-independent measure of systolic function, as well as diastolic function and ventriculoarterial coupling. Heart rate, myocardial oxygen consumption, and arrhythmia incidence were furthermore increased in the epinephrine group. Conversely, phenylephrine, a peripheral [alpha]-agonist, exhibited deleterious effects on systolodiastolic function and ventriculoarterial coupling. Conductance catheter and positron emission tomography yielded identical results with regard to myocardial function evolution under vasopressor treatment.

Conclusions: Phenylephrine, a drug without [beta]-1 effects, was associated with decreased ventricular performance and ventriculoarterial uncoupling, whereas epinephrine and norepinephrine improved global hemodynamics and myocardial function in severely hypokinetic and hypotensive experimental septic shock. Nevertheless, epinephrine was associated with increased myocardial oxygen consumption. Thus, norepinephrine appears to be a more reliable and safer strategy as a first-line therapy in this particular setting.

Anesthesiology. 2012 May;116(5):1083-1091

Lung ultrasound for pneumothorax by paramedics

May 20, 2012 by  
Filed under All Updates, EMS, Trauma, Ultrasound

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This UK study showed that paramedics could successfully acquire and identify lung ultrasound images after a two day course. The course covered the identification and management of patients who present with serious thoracic injury, with a specific focus on the use of thoracic ultrasound during early prehospital assessment. Standard 2D images for pleural sliding and comet tails and M-Mode for the ‘seashore sign’ were acquired, and colour Doppler was also used to assist in the identification of pleural sliding.


Objective This trial investigated whether advanced paramedics from a UK regional ambulance service have the ability to acquire and interpret diagnostic quality ultrasound images following a 2-day programme of education and training covering the fundamental aspects of lung ultrasound.

Method The participants were tested using a two-part examination; assessing both their theoretical understanding of image interpretation and their practical ability to acquire diagnostic quality ultrasound images. The results obtained were subsequently compared with those obtained from expert physician sonographers.

Results The advanced paramedics demonstrated an overall accuracy in identifying the presence or absence of pneumothorax in M-mode clips of 0.94 (CI 0.86 to 0.99), compared with the experts who achieved 0.93 (CI 0.67 to 1.0). In two-dimensional mode, the advanced paramedics demonstrated an overall accuracy of 0.78 (CI 0.72 to 0.83), compared with the experts who achieved 0.76 (CI 0.62 to 0.86). In total, the advanced paramedics demonstrated an overall accuracy at identifying the presence or absence of pneumothorax in prerecorded video clip images of 0.82 (CI 0.77 to 0.86), in comparison
with the expert users of 0.80 (CI 0.68 to 0.88). All of the advanced paramedics passed the objective structured clinical examination and achieved a practical standard considered by the examiners to be equivalent to that which would be expected from candidates enrolled on the thoracic module of the College of Emergency Medicine level 2 ultrasound programme.

Conclusion This trial demonstrated that ultrasound-naive practitioners can achieve an acceptable standard of competency in a simulated environment in a relatively short period of time.

Acquisition and interpretation of focused diagnostic ultrasound images by ultrasound-naive advanced paramedics: trialling a PHUS education programme
Emerg Med J, 2012 vol. 29 (4) pp. 322-326

Prehospital burn management in a combat zone.

May 18, 2012 by  
Filed under All Updates, EMS, Guidelines, Resus, Trauma

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A military study revealed troops suffering from severe burns tended to receive either no prehospital fluid or too much fluid1.

The authors point out some practical realities and an attempted solution:


For a medic potentially treating multiple casualties at once in a hostile environment, the calculation of the modified Brooke or Parkland formula may be unrealistic prior to beginning fluid resuscitation in the prehospital setting.

The USAISR’s Rule of 10 is a simplified formula to guide the initial fluid resuscitation of a burn victim. The burn size is estimated to the nearest 10% TBSA. For patients weighing 40 to 80 kg, the burn size is then multiplied by 10 to give the initial fluid rate in milliliters per hour. The rate is increased by 100 mL/hour for every 10 kg above 80 kg in terms of the patient’s weight. For the majority of adult burn patients, the Rule of 10 approximates the initial fluid rate within accepted ABA guidelines.


A previous study on the rule of 10 showed it provided an estimate that fell between the modified Brooke and Parkland estimates 87.8% of the time, less than the modified Brooke <12% of the time, and hardly ever (>1%) exceeded the Parkland estimate2.


OBJECTIVE: The purpose of this article is to provide a descriptive study of the management of burns in the prehospital setting of a combat zone.

METHODS: A retrospective chart review was performed of U.S. casualties with >20% total-body-surface-area thermal burns, transported from the site of injury to Ibn Sina Combat Support Hospital (CSH) between January 1, 2006, and August 30, 2009.

RESULTS: Ibn Sina CSH received 225 burn casualties between January 2006 and August 2009. Of these, 48 met the inclusion criteria. The mean Injury Severity Score was 31.7 (range 4 to 75). Prehospital vascular access was obtained in 24 casualties (50%), and 20 of the casualties received fluid resuscitation. Out of the 48 casualties enrolled, 28 (58.3%) did not receive prehospital fluid resuscitation. Of the casualties who received fluid resuscitation, nearly all received volumes in excess of the guidelines established by the American Burn Association and those recommended by the Committee for Tactical Combat Casualty Care. With regard to pain management in the prehospital setting, 13 casualties (27.1%) received pain medication.

CONCLUSIONS: With regard to the prehospital fluid resuscitation of primary thermal injury in the combat zone, two extremes were noted. The first group did not receive any fluid resuscitation; the second group was resuscitated with fluid volumes higher than those expected if established guidelines were utilized. Pain management was not uniformly provided to major burn casualties, even in several with vascular access. These observations support improved education of prehospital personnel serving in a combat zone.

1. Prehospital burn management in a combat zone
Prehosp Emerg Care, 2012 vol. 16 (2) pp. 273-276

2. Simple derivation of the initial fluid rate for the resuscitation of severely burned adult combat casualties: in silico validation of the rule of 10
J Trauma. 2010 Jul;69 Suppl 1:S49-54

End-Tidal CO2 as a Predictor of Cardiac Arrest Survival

May 16, 2012 by  
Filed under Acute Med, All Updates, EMS, ICU, Resus



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

Nebulised naloxone

May 14, 2012 by  
Filed under Acute Med, All Updates, EMS, Resus

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

Out-of hospital traumatic paediatric cardiac arrest

May 12, 2012 by  
Filed under All Updates, EMS, Kids, Resus, Trauma

This small study on traumatic arrests in children1 refutes the “100% mortality from traumatic arrest” dogma that people still spout and gives information on the mechanisms associated with survival: drowning and strangulation were associated with greater rates of survival to hospital admission compared with blunt, penetrating, and other traumas. Overall, drowning had the greatest rate of survival to discharge (19.1%).

I would like to know the injuries sustained in non-survivors, to determine whether they were potentially treatable. Strikingly, in the list of prehospital procedures performed, there were NO attempts at pleural decompression, something that is standard in traumatic arrest protocols in prehospital services were I have worked.

It is interesting to compare these results with those of the London HEMS team2, who for traumatic paediatric arrest achieved 19/80 (23.8%) survival to discharged from the emergency department and 7/80 (8.75%) survival to hospital discharge. They also noted a large proportion of the survivors suffered hypoxic or asphyxial injuries, whereas those patients with hypovolaemic cardiac arrest did not survive.


OBJECTIVE:To determine the epidemiology and survival of pediatric out-of-hospital cardiac arrest (OHCA) secondary to trauma.

METHODS:The CanAm Pediatric Cardiac Arrest Study Group is a collaboration of researchers in the United States and Canada sharing a common goal to improve survival outcomes for pediatric cardiac arrest. This was a prospective, multicenter, observational study. Twelve months of consecutive data were collected from emergency medical services (EMS), fire, and inpatient records from 2000 to 2003 for all OHCAs secondary to trauma in patients aged ≤18 years in 36 urban and suburban communities supporting advanced life support (ALS) programs. Eligible patients were apneic and pulseless and received chest compressions in the field. The primary outcome was survival to discharge. Secondary measures included return of spontaneous circulation (ROSC), survival to hospital admission, and 24-hour survival.

RESULTS:The study included 123 patients. The median patient age was 7.3 years (interquartile range [IQR] 6.0-17.0). The patient population was 78.1% male and 59.0% African American, 20.5% Hispanic, and 15.7% white. Most cardiac arrests occurred in residential (47.1%) or street/highway (37.2%) locations. Initial recorded rhythms were asystole (59.3%), pulseless electrical activity (29.1%), and ventricular fibrillation/tachycardia (3.5%). The majority of cardiac arrests were unwitnessed (49.5%), and less than 20% of patients received chest compressions by bystanders. The median (IQR) call-to-arrival interval was 4.9 (3.1-6.5) minutes and the on-scene interval was 12.3 (8.4-18.3) minutes. Blunt and penetrating traumas were the most common mechanisms (34.2% and 25.2%, respectively) and were associated with poor survival to discharge (2.4% and 6.5%, respectively). For all OHCA patients, 19.5% experienced ROSC in the field, 9.8% survived the first 24 hours, and 5.7% survived to discharge. Survivors had triple the rate of bystander cardiopulmonary resuscitation (CPR) than nonsurvivors (42.9% vs. 15.2%). Unlike patients sustaining blunt trauma or strangulation/hanging, most post-cardiac arrest patients who survived the first 24 hours after penetrating trauma or drowning were discharged alive. Drowning (17.1% of cardiac arrests) had the highest survival-to-discharge rate (19.1%).

CONCLUSIONS:The overall survival rate for OHCA in children after trauma was low, but some trauma mechanisms are associated with better survival rates than others. Most OHCA in children is preventable, and education and prevention strategies should focus on those overrepresented populations and high-risk mechanisms to improve mortality.

1. Epidemiology of out-of hospital pediatric cardiac arrest due to trauma
Prehosp Emerg Care, 2012 vol. 16 (2) pp. 230-236

2. Outcome from paediatric cardiac arrest associated with trauma
Resuscitation. 2007 Oct;75(1):29-34

Nitrate bolus in acute heart failure

May 7, 2012 by  
Filed under Acute Med, All Updates, ICU, Resus

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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

Passive leg raise predicted fluid responsiveness in kids

May 5, 2012 by  
Filed under All Updates, ICU, Kids

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Passive leg raising (PLR) is a great ‘free reversible fluid challenge’ to see if a shocked or hypotensive patient is likely to respond to volume therapy. A new study assesses its applicability in children.

PLR predicted fluid responders with 85% specificity but a lack of response did not rule out fluid responsiveness. Also, the effect of the PLR on cardiac index measured by echocardiography was the only way of predicting response – there was no relation to the more easily monitored effects of PLR on systolic blood pressure or heart rate.

Want to learn how to measure cardiac output using ultrasound? Mike Mallin from the Emergency Ultrasound Podcast shows you how here


OBJECTIVE: Fluid challenge is often used to predict fluid responsiveness in critically ill patients. Inappropriate fluid expansion can lead to some unwanted side effects; therefore, we need a noninvasive predictive parameter to assess fluid responsiveness. We want to assess the hemodynamic parameter changes after passive leg raising, which can mimic fluid expansion, to predict fluid responsiveness in pediatric intensive care unit patients and to get a cutoff value of cardiac index in predicting fluid responsiveness in pediatric patients.

DESIGN: Nonrandomized experimental study.

SETTING: Tertiary academic pediatric intensive care.

PATIENTS: Children admitted to pediatric intensive care.

INTERVENTION: Hemodynamic parameters were assessed at baseline, after passive leg raising, at second baseline, and after volume expansion (10 mL/kg normal saline infusion over 15 mins).

MEASUREMENTS AND MAIN RESULTS: We measured the heart rate, systolic blood pressure, and stroke volume and cardiac index using Doppler echocardiography. The hemodynamic parameter changes induced by passive leg raising were monitored. Among 40 patients included in the study, 20 patients had a cardiac index increase of ≥10% after volume expansion (responders). Changes in heart rate, systolic blood pressure, and stroke volume after passive leg raising did not significantly relate to the response to volume expansion. There was significant relation between changes in cardiac index to predict fluid responsiveness (p = .012, r = .22, 95% confidence interval 1.529 to 31.37). A cardiac index increase by ≥10% induced by passive leg raising predicted preload-dependent status with sensitivity of 55% and specificity of 85% (area under the curve 0.71 ± 0.084, 95% confidence interval 0.546-0.874).

CONCLUSION: The concomitant measurements in cardiac index changes after the passive leg raising maneuver can be helpful in predicting who might have an increase in cardiac index with subsequent fluid resuscitation.

The role of passive leg raising to predict fluid responsiveness in pediatric intensive care unit patients.
Pediatric Critical Care Medicine. 13(3):e155-e160, May 2012