This page is a collection of recent ER literature summaries that may be of interest to the reader.

Ketamine Is Effective Adjunct to Morphine for Controlling Acute Pain

Morphine plus ketamine performed better than morphine alone in this randomized, double-blind study.

Researchers performed a double-blind, randomized, placebo-controlled trial to evaluate the safety and effectiveness of subdissociative dose ketamine as an adjunct to morphine for acute pain. Sixty adult patients presenting to a level II community teaching hospital with acute pain (defined as pain with a duration of 15 days or less) were randomized to receive 0.1 mg/kg of morphine plus either 0.3 mg/kg of ketamine or placebo infused over 15 minutes. Pain was assessed on a traditional 10-point scale before administration and every 15 minutes after administration for up to 2 hours.

Pain scores were significantly lower in the morphine/ketamine group than in the morphine/placebo group at both 15 minutes (median scores, 3.6 vs. 6.0) and 30 minutes (3.0 vs. 5.0) after administration. There was no statistically significant difference in adverse events between groups and no occurrence of emergence phenomena in the ketamine group. Patients in the ketamine group also reported a higher rate of satisfaction with pain control (mean satisfaction score, 8.57 vs. 6.05 on a 10-point Likert scale).

Low-Dose Ketamine for Pain: IV Push or Slow Infusion?

Neuropsychiatric side effects were more common with intravenous push administration, but does it matter?

At intravenous (IV) doses of 0.1–0.3 mg/kg, ketamine is a safe and effective analgesic. Adverse effects are minimal and include sedation and a feeling of disconnection from reality. Investigators compared the effectiveness and adverse effect burden of ketamine administration by IV push versus slow infusion in a randomized, placebo-controlled, double-dummy trial.

Forty-eight emergency department patients with acute pain received 0.3 mg/kg of IV ketamine given either over 5 minutes by push or over 15 minutes by infusion. Feelings of unreality (quantified using the Side Effects Rating Scale for Dissociative Anesthetics) were more common in the IV push group overall (92% vs. 54%). Sedation was more pronounced in the IV push group, with median Richmond Agitation-Sedation Scale values at 5 minutes of −2 versus 0. The groups were comparable in terms of analgesic efficacy, but feelings of unreality were more pronounced in the IV push route at all time points

Ketamine as a First-Line Agent for Sedation of Agitated Patients?

A small study suggests that ketamine is more effective than alternatives; larger studies are needed to assess safety

Ketamine has a long history as a veterinary tranquilizer and is familiar to emergency physicians because it is a frequently used, safe, effective agent for procedural sedation and rapid sequence intubation. But can it be used to control behavior in severely agitated patients? In a prior summary of a study on this topic (NEJM JW Emerg Med Mar 2016 and Ann Emerg Med 2016; 67:581), we raised concerns about ketamine's propensity to cause endogenous catecholamine release — what might happen when agitated patients are exposed to even more catecholamines? Now investigators report on a small prospective observational study comparing five regimens for sedation of acutely agitated patients: ketamine (24 patients), lorazepam (33), midazolam (17), haloperidol (14), or haloperidol plus lorazepam or midazolam (10).

Doses and routes of administration varied widely. Effectiveness was superior with ketamine, with a mean time to perceived adequate sedation of 6.6 minutes, versus 18, 15, 13, and 23 minutes with the other regimens, respectively. Adverse events, requirements for redosing, and changes in vital signs were similar among the groups, except that two patients in the ketamine group were intubated, versus one in each of the other groups.

Dose of ketamine for agitation/delerium 4-5 mg/kg IM

No Threshold for Hypotension in Patients with Traumatic Brain Injury

Mortality decreased with increasing prehospital blood pressures, even for patients who would not be considered hypotensive.

Prior studies have shown that even a single episode of prehospital hypotension or hypoxia increases mortality in patients with traumatic brain injury (TBI). Based on studies that dichotomized patients using various thresholds of systolic blood pressure (SBP), some guidelines define hypotension as SBP <90 mm Hg and provide corresponding treatment recommendations.

These authors questioned whether that threshold of 90 mm Hg represents a true inflection point for mortality or whether mortality continues to decline with even higher SBPs. In an observational study, they examined the relationship between in-hospital mortality and prehospital systolic blood pressures ranging from 40 to 119 mm Hg in a cohort of 3844 patients aged 10 years and older with TBI who were transported by Arizona emergency medical services.

Using robust statistical methods, the investigators demonstrated no threshold or inflection point for the relationship between mortality and SBP. At every 10-mm Hg interval of SBP from 40 to 119 mm Hg, mortality decreased when pressure was higher and increased when pressure was lower (adjusted odds ratio, 0.81 for each 10-mm Hg pressure increase)

Crank up the Oxygen and Skip the Bag-Valve-Mask

 Driver BE et al. Ann Emerg Med 2017 Jan.
High-flow oxygen through a nonrebreather mask is noninferior to bag-valve-mask for preoxygenation.

Preoxygenation is a key step in rapid sequence intubation and involves allowing the patient to breath spontaneously with supplemental oxygen. The classic method, thought to achieve the highest alveolar oxygen concentration, is to use a bag-valve-mask (BVM) with high-flow oxygen and a good mask seal but no positive pressure (i.e., no squeezing of the bag). These investigators assessed whether preoxygenation with a nonrebreather mask delivering high-flow oxygen is noninferior to preoxygenation with a BVM delivering oxygen at 15 L/minute.

Twenty-six healthy volunteers were preoxygenated with each of four methods in random order: nonrebreather mask with 15 L/minute oxygen flow; nonrebreather mask with the wall-mounted oxygen valve wide open (>40 L/minute flow); BVM with 15 L/minute oxygen flow, and standard mask with the wall-mounted oxygen valve wide open. The corresponding mean fractions of expired O2 in a single breath were 54%, 86%, 77%, and 72%

Comment by  Daniel J. Pallin, MD, MPH

The traditional BVM method is uncomfortable for patients because someone has to hold the mask tightly over the patient's face. Also, in my experience, this method is rarely used correctly, in that everyone seems to feel a compulsion to squeeze the bag, which risks filling the stomach with air and increasing the incidence of vomiting and aspiration.

This study shows that high-flow oxygen through a nonrebreather mask is not inferior to the BVM approach. However, it is unknown if optimizing preoxygenation influences patient outcomes, so it's hard to know what to recommend — a nonrebreather mask at 15 L/minute might be adequate for most intubations. Having read this study, I will no longer preoxygenate with a BVM. Instead, I will use a nonrebreather mask at 15 L/minute and then will open the oxygen valve to maximize flow during the last 3 minutes (or 8 tidal volume breaths for cooperative patients).

Should We Treat Patients with Isolated Calf Deep Venous Thrombosis?

In a randomized trial, treatment did not improve outcomes.

For isolated deep venous thrombosis (DVT) of the calf, American College of Chest Physicians guidelines suggest (1) anticoagulation in patients with severe symptoms or risk factors for proximal extension, and (2) in lower-risk patients, repeat ultrasound imaging during 2 weeks, plus anticoagulation for those whose DVTs extend proximally (Chest 2016; 149:315). However, data to inform these decisions are limited. In this double-blind trial, researchers in Europe randomized 259 adults with first acute isolated symptomatic calf DVTs, diagnosed by ultrasound, to receive either the low-molecular-weight heparin nadroparin (not available in the U.S.) or placebo for 6 weeks; follow-up visits with repeat ultrasound were scheduled at 3 to 7 days and at 6 weeks. Patients with active cancer or previous venous thromboembolic disease were excluded. About half of the patients had reversible risk factors (i.e., estrogen therapy or recent surgery, immobilization, or prolonged travel).

The primary composite outcome (proximal extension of calf DVT, contralateral proximal DVT, or pulmonary embolism at 6 weeks) occurred in 3% of nadroparin patients and 5% of placebo patients — a non-significant difference. Outcomes were similar at 3 months. Major bleeding occurred in 4% of nadroparin patients and no placebo patients (P=0.03). No participant died.


According to the authors, this study is the first placebo-controlled, randomized treatment trial for isolated calf DVT. The results suggest that, for patients like those enrolled in this trial, initial anti-coagulation is unnecessary if a second ultrasound examination is done within a week to screen for proximal extension. With its sample size, the study was underpowered to detect a several percentage point benefit for anti-coagulation, but it did remind us of bleeding risks during an even relatively brief course of anti-coagulation.

Comparison of Temperature Acquisition Methods in the ED

In a study of 987 emergency department (ED) patients (mean age 55 years, 65% female) who received a rectal temperature measurement as part of routine care, researchers assessed the accuracy of oral, tympanic membrane, and temporal artery thermometry.

Overall, the noninvasive temperature readings were inaccurate; they differed by ≥0.5°C from rectal temperatures 36% of the time and from oral temperatures 50% of the time. The most accurate noninvasive method was tympanic membrane thermometry.

The sensitivity and specificity for detecting fever of 38°C or higher measured rectally were as follows:
       Tympanic membrane: 68% and 98%
       Temporal artery: 71% and 92%
       Oral: 37% and 99%

When the cutoff temperature for defining fever was lowered to 37.5°C, the sensitivity and specificity were as follows:
       Tympanic membrane: 91% and 90%
       Temporal artery: 91% and 72%
       Oral: 58% and 97%

Comment: Accurate temperature measurement can be important to patient care. Rectal temperatures have long been considered the gold standard for accurate thermometry, but it is not feasible or appropriate for evaluation of all acute care patients. If hospitals want to continue to use noninvasive modes for temperature collection, then a cutoff value of 37.5°C should be used to define fever, or at least to trigger taking a rectal temperature

Tamsulosin Facilitates Passage of Ureteral Stones 4–10 mm in Size

Are IV Fluids Helpful for Migraine?

An observational study suggests not.

Recommended medications for migraine treatment include triptans, nonsteroidal anti-inflammatory agents, prochlorperazine or metoclopramide, and caffeine. All can be given orally, subcutaneously, or intramuscularly. No evidence supports the placement of intravenous (IV) catheters in migraine patients.

In a post-hoc observational study of data from four emergency department-based randomized trials of IV metoclopramide, investigators compared outcomes between 120 participants who received IV fluids at the treating physician's discretion and 458 who did not. At 1 hour, patients who received IV fluids had less improvement in pain than those who did not receive IV fluids (improvement of 4.5 vs. 5.1 points on a 0-to-10-point scale).

Obviously, this observational study is limited by confounding by indication, since patients receiving IV fluids may have differed from those not receiving IV fluids. Nevertheless, the result calls into question the habitual — and non–evidence-based — practice of administering fluids and drugs intravenously to migraine patients (and many others, for that matter). I think the best treatment is subcutaneous sumatriptan, if the migraine has not been present for more than a few hours, or intramuscular prochlorperazine plus oral ibuprofen and caffeine, or all of the above.

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Meta-Analysis Suggests Ketofol Is Safer Than Propofol Alone

Pooling of data from several trials suggests fewer respiratory and cardiovascular adverse events with ketofol.

Investigators conducted a meta-analysis of randomized trials comparing ketofol (a 1:1 or 1:4 combination of ketamine and propofol) to propofol alone for procedural sedation in adults to compare adverse events associated with the two approaches.

Eighteen studies involving roughly 2100 adult patients were included in the pooled analysis. With ketofol, compared to propofol, the risk of respiratory suppression requiring an intervention was 0.47 in the 14 trials that measured this outcome, the risk of hypotension was 0.41 in 9 trials, and the risk of bradycardia was 0.47 in 8 trials. Nausea and psychomimetic complications did not differ between the pooled ketofol and propofol groups.

Propofol is very safe, and the transitory respiratory or cardiovascular suppression that often occurs should not keep us from using it. Nevertheless, this meta-analysis suggests that ketofol might be safer. A single large randomized trial would be valuable. Nonetheless, based on provider discretion, either approach is perfectly appropriate now

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Does Nasal cannula oxygen improve preoxygenation for intubation?

Hayes-Bradley C et al. Ann Emerg Med 2015 Dec 31.
Adding nasal cannula to nonrebreather mask or bag-valve-mask preoxygenation improved end-tidal oxygen levels.

Preoxygenation is used to fill the lungs with oxygen and wash out nitrogen before emergency endotracheal intubation. Investigators assessed the contribution of supplemental nasal cannula–delivered oxygen to end-tidal oxygen levels in a randomized crossover trial of 60 healthy volunteers who received either bag-valve-mask or nonrebreather mask ventilation in each of four scenarios: with and without nasal cannula oxygen and with and without mask leak. End-tidal oxygen levels were measured after 3 minutes of preoxygenation.

Oxygenation was not improved by the addition of nasal cannula oxygen to bag-valve-mask ventilation in the absence of mask leak. However, the addition of nasal cannula oxygen did improve oxygenation in the other scenarios: bag-valve-mask with leak (mean end-tidal oxygen, 66% with nasal cannula oxygen vs. 41% without) nonrebreather mask with leak (65% vs. 48%), and nonrebreather mask without leak (67% vs. 52%).

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Inhalation of Isopropyl Alcohol Alleviates Nausea in ED Patients

Beadle KL et al. Ann Emerg Med 2015 Dec 8.

Breathing with an alcohol wipe in front of the nose was more effective than breathing with a saline wipe.

Prior research has found antiemetics to be no more effective than placebo in emergency department (ED) patients with nausea (NEJM JW Emerg Med Aug 2014 and Ann Emerg Med 2014 May 9; [e-pub]). In the current study, investigators at a single academic ED randomized a convenience sample of 80 adult patients with nausea or vomiting to hold either a standard isopropyl alcohol wipe or a saline wipe 2.5 cm from the nose and breathe deeply for up to 1 minute. The intervention was repeated three times at 2-minute intervals. Patients rated nausea on an 11-point scale (with a score of 0 indicating no nausea) at baseline and 2, 4, 6, and 10 minutes after the start of the intervention.

Even though nausea was a little worse in the intervention group at baseline (median nausea score, 7 vs. 6), at 10 minutes the intervention group had less nausea than the placebo group (median score, 3 vs. 6).

These are promising initial data. Breathing with an alcohol pad in front of the nose seems to be a safe and effective short-term treatment for nausea. Interestingly, the investigators note that other forms of “aromatherapy,” such as peppermint oil, might be as effective. More data are needed to evaluate the longer-term effects of such interventions, and it's a shame that the investigators only collected outcome data at 10 minutes. However, the intervention would be easy to repeat periodically. It just might be worth a try.

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So this article came out in August 2015, basically showing that ANY interruption in cardiac compressions were bad.

Brouwer TF et al. Circulation 2015 Aug 7.

Longer pauses in chest compressions were associated with lower survival in patients with ventricular fibrillation cardiac arrest. Current cardiopulmonary resuscitation (CPR) guidelines emphasize continuous compressions with minimal interruptions. The focus has been on minimizing perishock pauses, as these were the types of pauses most easily measured during ongoing resuscitations. However, impedance recording capabilities of newer defibrillators allow measurement of all interruptions. To determine whether pauses for any reason are associated with reduced survival, researchers reviewed all cases of ventricular fibrillation out-of-hospital cardiac arrest in Amsterdam in 2009 for which all continuous impedance recordings were available (including from public access defibrillators). A total of 319 patients were included, with an overall survival to hospital discharge of 38%. A multivariate regression model demonstrated decreased odds of survival for each 5-second increase in the longest chest compression pause (odds ratio, 0.89). The longest pause was for reasons other than shock delivery in 36% of patients; survival was lower in these patients than in those whose longest pause was associated with defibrillation (27% vs. 44%). Comment – NEJM reviewer Ali Raja CPR shouldn't be paused for anything except defibrillation, and even those pauses should be very brief. Non-shock pauses (e.g., for intubation) are clearly associated with worse patient outcomes, and we should aim to minimize or eliminate them from our patients' resuscitations

Then this article, published in November 2015, showed a completely different result?

Similar Survival Rates with Continuous or Interrupted CPR for Out-of-Hospital Cardiac Arrest

Nichol G et al. N andEngl J Med 2015 Nov 9. Koster RW. N Engl J Med 2015 Nov 9.

Both groups in this randomized trial received very high-quality compressions. Recent American Heart Association guidelines recommend changes to cardiopulmonary resuscitation (CPR) including that compressions be fast (100–120/minute), deep (5–6 cm), and continuous (NEJM JW Emerg Med Dec 2015 and Circulation 2015; 132[Suppl 2]:S315). However, the recommendation about compressions was based on retrospective cohort and animal studies and prospective studies involving multi-intervention bundles. To tease out whether continuous compressions independently improve survival in out-of- hospital cardiac arrest, Resuscitation Outcomes Consortium investigators performed a cluster randomized trial involving 114 emergency medical services agencies in North America. They randomized adults with nontraumatic cardiac arrest to receive continuous compressions (100 compressions/minute with asynchronous positive-pressure ventilation at 10 ventilations/minute) or interrupted compressions (30 compressions followed by 2 positive-pressure ventilations). Other basic and advanced life support interventions were not standardized. Of 23,711 patients analyzed, 53% received continuous compressions. Rates of survival to hospital discharge (the primary outcome) were similar in the continuous- and interrupted-compression groups (9.0% and 9.7%, P=0.07), as were rates of survival with favorable neurologic function (7.0% and 7.7%). Compressions were delivered in the two groups at similar depth (mean, 4.8 and 4.9 cm, respectively) and speed (mean, 110 and 109/minute, respectively). Mean pre- and post-shock pauses were the same in the two groups (pre-shock, 12 seconds; post-shock, 6 seconds). Comment: NEJM reviewer Ali Raji This well-done study demonstrates that continuous and interrupted high-quality compressions are equally effective. The take-home message is that high-quality CPR saves lives, regardless of compression strategy.

Am J Respir Crit Care Med. 2015 Oct 1.

Randomized Trial of Apneic Oxygenation during Endotracheal Intubation of the Critically Ill.

Semler, Matt et al.

Hypoxemia is common during endotracheal intubation of critically ill patients and may predispose to cardiac arrest and death. Administration of supplemental oxygen during laryngoscopy (apneic oxygenation) may prevent hypoxemia.


To determine if apneic oxygenation increases the lowest arterial oxygen saturation experienced by patients undergoing endotracheal intubation in the intensive care unit.


A randomized, open-label, pragmatic trial in which 150 adults undergoing endotracheal intubation in a medical intensive care unit were randomized to receive 15 L/min of 100% oxygen via high-flow nasal cannula during laryngoscopy (apneic oxygenation) or no supplemental oxygen during laryngoscopy (usual care). The primary outcome was lowest arterial oxygen saturation between induction and two minutes after completion of endotracheal intubation.


Median lowest arterial oxygen saturation was 92% with apneic oxygenation versus 90% with usual care (95% confidence interval for the difference -1.6% to 7.4%; P = .16). There was no difference between apneic oxygenation and usual care in incidence of oxygen saturation < 90% (44.7% versus 47.2%; P = .87), oxygen saturation < 80% (15.8% versus 25.0%; P = .22), or decrease in oxygen saturation > 3% (53.9% versus 55.6%; P = .87). Duration of mechanical ventilation, intensive care unit length of stay, and in-hospital mortality were similar between study groups.


Apneic oxygenation does not appear to increase lowest arterial oxygen saturation during endotracheal intubation of critically ill patients compared to usual care. These findings do not support routine use of apneic oxygenation during endotracheal intubation of critically ill adults.

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