In the June edition of the articles of the month, I included a paper on hypertonic saline for the treatment of traumatic brain injury. My conclusion (and that of the paper’s authors) was that hypertonic saline did not seem to provide any benefit, either in terms of mortality, or even in terms of lowering intracranial pressure. My friend Scott Weingart pointed out that the paper might not actually support that conclusion. The problem was with the studies they included in the review (which I hadn’t read myself). This is probably an excellent lesson: reviews are nice as an introduction to a topic, but expert clinical practice really requires a familiarity with the original literature. For example, there are many reviews that conclude that tPa is excellent for ischemic stroke, but… well I guess I won’t get into that here. Anyhow, I promised to read the studies on hypertonic saline in a little more depth and post an update, so that is what follows.
A monthly summary and brief critical appraisal of the best emergency medicine literature I have encountered
Biggest non-news of the month
ATTACH-2 trial: Qureshi AI, Palesch YY, Barsan WG. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. The New England journal of medicine. 2016. PMID: 27276234 [free full text]
To date, all the evidence available has indicated no clinically important benefit to lowering blood pressure in people with head bleeds. However, evidence is never enough to stop people from talking about how much an intervention “makes sense”. This is a large, randomized, multi-center, open-label trial that compared intensive blood pressure management (target systolic 110-139) to standard BP management (target 140-179) in 1000 patients with acute intracranial hemorrhage. To get into the trial, you needed at least one systolic blood pressure measurement over 180. Blood pressure was maintained in the target zone for 24 hours after enrollment. The primary outcome was 90 day death or disability, represented by a modified Rankin score of 4-6, and was the same for both groups (38.7% intensive vs 37.7% standard). There were no important differences in secondary outcomes. Despite the excitement for intensive treatment that somewhat inexplicably sprang from previous negative trials, like INTERACT-2, this negative finding is in keeping with all the evidence on this topic to date. Although both groups here were managed to some target, it’s not clear to me that any blood pressure management is really required. As long as you remember to treat their pain, the blood pressure generally normalizes anyway.
Bottom line: There is no need to aggressively manage blood pressure in patients with head bleeds.
You don’t remember INTERACT-2?
Anderson CS, Heeley E, Huang Y. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. The New England journal of medicine. 368(25):2355-65. 2013. PMID: 23713578 [free full text]
This is a multi-center, randomized, partially blinded trial comparing intensive blood pressure control (target of a systolic pressure <140 within 1 hour) to guideline recommended care (to a target systolic <180) in 2794 adult patients with intracerebral hemorrhage within the last 6 hours. It was a negative trial, with the primary outcome of death or disability (modified Rankin score 3-6) at 90 days of 52.0% in the intensive group and 55.6% in guideline group (p=0.06, OR 0.87, 95%CI 0.75-1.01). This is obviously pretty close to statistically significant, and a secondary outcome using the relatively controversial ordinal analysis was statistically significant, so a lot of people seemed to overlook the fact that it was a negative trial. Interpreted in isolation, you might think that this could be a positive result trying to escape our slavish devotion to p values, but in the larger context of the recurrent negative trials, this is just another negative trial.
Bottom line: There is no evidence out there that really supports aggressive blood pressure control in patients with head bleeds.
OK – blood pressure might not help, but surely brains need salt?
Berger-Pelleiter E, Émond M, Lauzier F, Shields JF, Turgeon AF. Hypertonic saline in severe traumatic brain injury: a systematic review and meta-analysis of randomized controlled trials. CJEM. 18(2):112-20. 2016. PMID: 26988719
I have heard hypertonic saline mentioned as a replacement for mannitol for the treatment of intracranial hypertension at numerous conferences since finishing residency. I was under the impression it was becoming the treatment of choice, but there is a reason we practice evidence based medicine. This is a systematic review and meta-analysis that identified 11 RCTs covering 1820 adult patients with traumatic brain injury comparing hypertonic saline to either mannitol (½ the studies) or another solution (often normal saline, or even hypotonic saline.) Hypertonic saline did not decrease mortality (RR 0.96, 95%CI 0.83-1.11). It didn’t lower intracranial pressure (weighted mean difference -0.39, 95%CI -3.78 – 2.99). And it didn’t improve functional outcomes (RR 1.12, 95% CI 0.92-1.36). Having the same outcomes as mannitol may not be bad, but in ½ these studies hypertonic saline was compared to iso or even hypotonic crystalloids (placebo?) and didn’t perform any better. On the other hand, it doesn’t look any worse than mannitol, so there still may be a role somewhere for it in trauma.
Bottom line: We probably shouldn’t be rushing to change to hypertonic saline in the management of traumatic brain injury.
EDIT: Scott Weingart has pointed out that the individual studies included in this review really weren’t designed to make the conclusions these authors make. (See the comments below). I haven’t read the individual studies yet, but once I do, I will provide an updated post on all the evidence for hypertonic saline.
We desperately need droperidol back
Meltzer AC, Mazer-Amirshahi M. For Adults With Nausea and Vomiting in the Emergency Department, What Medications Provide Rapid Relief? Annals of emergency medicine. 2016. PMID: 27130801
This is a systematic review of RCTs looking at the treatment of nausea and vomiting in the emergency department. They found 8 trials that covered 952 patients. The ONLY medication that demonstrated a statistically significant decrease in nausea at 30 minutes was droperidol. Metoclopramide, ondansetron, prochlorperazine, and promethazine were all statistically nondifferentiable from placebo, and even if you had larger numbers, the magnitude of change with those drugs is likely clinically insignificant (about 0.5/10 on a VAS). Droperidol decreased nausea by 1.6/10 at 30 minutes.
Bottom line: Once again, droperidol is a very valuable drug, that was taken away from us for no good reason.
Single dose dex for asthma – again
Rehrer MW, Liu B, Rodriguez M, Lam J, Alter HJ. A Randomized Controlled Noninferiority Trial of Single Dose of Oral Dexamethasone Versus 5 Days of Oral Prednisone in Acute Adult Asthma. Annals of emergency medicine. 2016. PMID: 27117874
Have I beat this one to death yet? A steroid is a steroid is a steroid. However, the previous papers I have covered on this topic were in children – so I’ll throw this in. This is a randomized, double-blind, non-inferiority trial comparing a single dose of dexamethasone (12mg) to a 5 day course of 60mg of prednisone in 376 adult emergency patients with asthma exacerbations. The primary outcome of recidivism at 14 days was essentially the same (12.1% vs 9.8%, 95%CI -4.1 to 8.6%). However, because they defined non-inferiority as 8%, and the confidence interval is relatively wide, they cannot conclude that dexamethasone is noninferior. Personally, I think based on those numbers it probably is going to be, and that this trial was just under powered – but perhaps we should be giving a second dose of dex the next day.
Bottom line: Single dose dexamethasone is probably just as good as 5 days of prednisone in adults with asthma.
Can’t touch this (Stop. Hammer time.)
Ferguson CM, Swaroop MN, Horick N. Impact of Ipsilateral Blood Draws, Injections, Blood Pressure Measurements, and Air Travel on the Risk of Lymphedema for Patients Treated for Breast Cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology.34(7):691-8. 2016. PMID: 26644530
Physiologically speaking, I could never quite understand why I was supposed to avoid drawing blood or measuring blood pressures in the arm that a breast cancer patient had axiallry lymph node dissection on. It is supposed to be a disaster resulting in lymphedema, and patients can get very angry if you try – but what exactly was the mechanism of disaster? Well, maybe there isn’t one. This is a prospective study of postoperative breast cancer patients being screened for lymphadenopathy, comparing patients who had blood draws, blood pressure measurement, injections, trauma, and cellulitis in the affected arm to those who didn’t. They also compared number of times on an airplane. The biggest weakness in this data is that although the lymphedema data was collected prospectively, data about the exposures was based on patient report and is therefore subject to recall bias. None of venipuncture, injection, or blood pressure measurements had any association with lymphedema. For patient information, the number of flights and length of flights were also not associated with lymphedema. This data is not enough to prove safety, but given the dubious physiologic explanation, this is reassuring.
Bottom line: You are unlikely to cause lymphedema by doing simple ED procedures such as injections, blood draws, or blood pressure measurements.
Hippocrates has still got it
Another gem from the BMJ Christmas edition. One of Hippocrates’s aphorisms was: “It augurs well, if the patient’s mind is sound, and he accepts all food that’s offered him; but, if the contrary conditions do prevail, the chances of recovery are slim”. In other words, good appetite and good cognition make survival more likely. Using data from the Manitoba Study of Health and Aging, a prospective cohort study, these authors tested that theory. Combined, poor appetite and poor cognition predicted death, with a hazard ratio of 2.37. Both components were individually predictive, with poor appetite and cognition having hazard ratios of 1.79 and 2.21 respectively. They conclude, “An aphorism devised by Hippocrates millennia ago can predict death in the modern era.”
Bottom line: Hippocrates was probably a better clinician than all of us. (Also, these are important factors to think about when discussing end of life issues with our patients.)
Reminder: we treat patients, not numbers (times three)
Nakprasert P, Musikatavorn K, Rojanasarntikul D, Narajeenron K, Puttaphaisan P, Lumlertgul S. Effect of predischarge blood pressure on follow-up outcomes in patients with severe hypertension in the ED. The American journal of emergency medicine. 34(5):834-9. 2016. PMID: 26874395
This is a single center prospective observational study looking at 146 consecutive adult emergency department patients with a blood pressure ≥ 180/110 and no acute end-organ damage (the so called “hypertensive urgency”). One exclusion criteria that could be useful to you clinically was if patients had their BP decrease to less than 180 with just 10 minutes of quiet bed rest, which happened in 16/221 (7%) of the patients screened. They compared patients who had a blood pressure less than 180 at the time of discharge (98 patients) to those who still had a pressure over 180 at discharge (48 patients). There were no differences between these two groups. In fact, only 1 patient (0.7%) had a “hypertension related adverse event”, and that was in the group with the lower blood pressure at discharge. (The adverse event was just a patient who returned with an asymptomatic 5cm descending thoracic aortic aneurysm for which no intervention was done.) This trial was nonrandomized, and almost everyone was given antihypertensives, even though we know there is no value and potential harm in asymptomatic patients. Also, it is really hard to draw conclusions from a trial with an event rate of 1. However, we already know that asymptomatic hypertension does not require ED treatment. This study tells you that there is no need to get a lower number recorded on the chart before discharge. The outcomes are the same.
Bottom line: Don’t treat asymptomatic hypertension, even if someone has used the utterly useless label “urgency”
Patel KK, Young L, Howell EH. Characteristics and Outcomes of Patients Presenting With Hypertensive Urgency in the Office Setting. JAMA internal medicine. 2016. PMID: 27294333
This is a retrospective, single-center cohort study of 59,535 patients with hypertensive “urgency” (systolic ≥180 and/or diastolic ≥110 but without symptoms) in an outpatient clinic. Apparently only 426 (0.7%) were referred into the emergency department, which either tells you this database is awful or the physicians are excellent. Major adverse cardiac events (MACE) at 30 days were 0.5% in the patients referred to the ED and 0.2% in those sent home (p=0.23). At 6 months, the numbers were 0.9% and 0.8% (p=0.83) respectively. They conclude: “referral to the ED was associated with increased use of health care resources but not better outcomes.”
Bottom line: There is no such thing as hypertensive “urgency”. Stop using the term. Stop treating the number.
(If any primary care physicians that end up reading this: asymptomatic patients DO NOT need to be sent to the emergency department because of high blood pressure, no matter what the number.)
Driver BE, Olives TD, Bischof JE, Salmen MR, Miner JR. Discharge Glucose Is Not Associated With Short-Term Adverse Outcomes in Emergency Department Patients With Moderate to Severe Hyperglycemia. Annals of emergency medicine. 2016. PMID: 27353284
This is another retrospective, single-center study looking at all patients presenting to the emergency department with a glucose above 22mmol/L (400mg/dL) and subsequently discharged. Patients with type 1 diabetes were excluded. They found 422 patients with 566 encounters for the chart review. Looking at the blood glucose level at the time of discharge, there was no difference in adverse events (primarily re-visits for hyperglycemia, without any consequence) whether you got the glucose level down during the visit or not. In fact, the mean discharge glucose level was lower in patients that had subsequent adverse events than those without (17.6mmol/L vs 18.6mmol/L). Only 2 patients had glucose related adverse events (0.4%), both DKA. Overall, the discharge glucose level was not associated with return visits, ED usages, or hospitalization.
Bottom line: We need to rule out underlying pathology in hyperglycemic patients, but there is no value in temporarily lowering glucose and getting a better number on the chart. These patients just need close follow-up.
How about a shot in the arm?
Kashani P, Asayesh Zarchi F, Hatamabadi HR, Afshar A, Amiri M. Intra-articular lidocaine versus intravenous sedative and analgesic for reduction of anterior shoulder dislocation. Turkish Journal of Emergency Medicine. 16(2):60-64. 2016. [free full text]
This is a randomized, controlled trial of 104 emergency department patients with anterior shoulder dislocations comparing intra-articular lidocaine (20ml of 1% lidocaine, landmark based) to intravenous procedural sedation for reduction. (The biggest weakness of the study is that they used midazolam (0.05mg/kg) and fentanyl (1mcg/kg) as their sedation agents, which most people don’t use any more, and have been shown to have a higher complication rate. The reductions were attempted 15 minutes after the shoulder injection. Pain scores were less during the reduction in the intra-articular lidocaine group (0.3/10 versus 3/10, p<0.001). Pain scores were the same post-reduction (1/10 in both groups). However, there were 9 patients in the injection group who were “completely dissatisfied” with their care, as compared to 0 in the sedation group. Adverse events were higher in the sedation group: there were 0 adverse events with the injections, versus 11% apnea and 10% hypoxia with the sedation. Those numbers are really high, and good reasons not to use the fentanyl/midaz combo. I have used intra-articular lidocaine a number of times, primarily ultrasound guided, and I like it – but I would still personally rather be sedated if my shoulder was out. I had been using this for post-reduction pain, but that was unchanged in this study.
Bottom line: Intra-articular lidocaine can definitely be used to reduce shoulder dislocations, but its exact role as compared to sedation still isn’t clear
LEMONS is a lemon?
Norskov AK, et al. Diagnostic accuracy of anaesthesiologists’ prediction of difficult airway management in daily clinical practice: a cohort study of 188 064 patients registered in the Danish Anaesthesia Database. Anaesthesia 2014. PMID: 25511370 [free full text]
We all know how to assess patients to predict a difficult airway – the classic LEMONS assessment – but are those assessments any good? This is a database study, looking at a cohort of 188,064 Danish anesthesia cases. There were 3391 difficult intubations, and 3154 (93%) were unanticipated. In 929 cases the anesthesiologists predicted difficult intubation, and it was only actually difficult in 229 (25%). Similarly, difficult bag valve mask ventilation was unanticipated in 808/857 (94%) of cases, and predictions of difficulty were only correct in 49/218 (22%).
Bottom line: We cannot predict difficult airways. Be prepared and have a set algorithm you are going to follow for every airway, no matter how easy you think it is going to be.
Obsessive twitter users beware
Alim-Marvasti A, Bi W, Mahroo OA, Barbur JL, Plant GT. Transient Smartphone “Blindness”. The New England journal of medicine. 374(25):2502-4. 2016. PMID: 27332920
I just found this case report interesting. They present 2 patients with transient monocular blindness. They had normal workups, but both patients experienced this after looking at their smartphones while lying in bed. They think that the blindness was the result of one eye being blocked by the pillow, so that it was dark-adapted, while the other was looking at the bright screen and therefore became light-adapted. When the phone was turned off, and both eyes were used in the dark room, the light-adapted eye was perceived as being blind for a number of minutes.
Bottom line: Physiology can still be interesting
Chest compressions can’t circulate blood you don’t have
Bowles F, Rawlinson K. BET 3: The efficacy of chest compressions in paediatric traumatic arrest. Emergency medicine journal : EMJ. 33(5):368. 2016. PMID: 27099381
Cardiac arrest means push hard and push fast. That has been branded into our grey matter. However, most trauma experts I have spoken with don’t think that there is much of a role for chest compressions in traumatic cardiac arrest. They just get in the way of what you really need to be doing, if there is any chance of salvage, which is opening the chest. However, my experience in community hospitals is that this distinction between traumatic and non-traumatic arrests is not well known. This is a review looking for evidence of the benefit of chest compressions in pediatric traumatic arrests. There is no evidence, so it’s not much of a paper. They just conclude that you should follow local guidelines. I see no reason that children should be different from adults in this scenario, but there also isn’t great evidence in adults.
Bottom line: We have no idea whether we should be doing chest compressions in traumatic cardiac arrest. Just make sure that your compressions don’t result in injuries to staff trying to perform important procedures.
The authors’ title is best: Docusate: A placebo pill for soft poops
Carbon J and Kolber M. Docusate: A placebo pill for soft poops. Tools for practice. Alberta College of Family Physicians. April 25, 2016. [free full text]
This review looked at whether docusate sodium (Colace) or docusate calcium (Surfak) are effective for prevention or treatment of constipation. They identified 3 RCTs of docusate versus placebo in functional or medication induced constipation, and all were negative. One RCT compared docusate to polyethylene glycol, and the polyethylene glycol resulted in a bowel movement 1-2 days earlier. Biggest limitation: these trials were not in emergency department patients.
Bottom line: There is probably no role for docusate in the management of constipation.
I know a number of people who like to chase their drugs with a good fatty meal – and now we can give it to them intravenously
Lam SH, Majlesi N, Vilke GM. Use of Intravenous Fat Emulsion in the Emergency Department for the Critically Ill Poisoned Patient. The Journal of emergency medicine. 2016. PMID: 26972018
This is a review, but not surprisingly, considering that it is a toxicology paper, they only found 1 RCT. The majority of the ‘evidence’ is from 4 retrospective cohorts, and 79 case reports. In other words, there really is no evidence – but we still need to know what to do, so here is what they suggest. They think intralipid therapy is ‘probably’ beneficial for all local anesthetic toxicity. (I reviewed that topic here.) There is a long list of drugs that they conclude may have a ‘possible benefit’, including amitriptyline, calcium channel blockers, cocaine, and beta-blockers – based entirely off low quality case reports. They suggest it should be used if the patient is hemodynamically unstable and not responding to standard resuscitation, and that the dose is 20% intravenous fatty emulsion as a 1.5 ml/kg bolus, then an effusion of 0.25ml/kg/min for up to 60 minutes. The bolus could be repeated once at 5 minutes.
Bottom line: In the dying tox patient, this might be worth a try. I would definitely use it with local anesthetic toxicity, but otherwise would probably speak with poison control.
Cheesy joke of the month
Doctor: Sir, were you using a condom during the last time you had sex?
Patient: Doctor, what do you mean by “the last time”!?
Thanks for reading. If you find these monthly summaries useful, or you know anyone else who might find them useful, please spread the word. I love doing this, but it is really only valuable if the information reaches people who might use it. On the other hand, if you have any suggestions for improvement or come across any articles that you think should be included, please feel free to contact me.