A multicentre RCT showed intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended. Magnesium for aneurysmal subarachnoid haemorrhage (MASH-2): a randomised placebo-controlled trial Lancet 2012 July 7; 380(9836): 44–49 Free full text Click to read abstract
Background Magnesium sulphate is a neuroprotective agent that might improve outcome after aneurysmal subarachnoid haemorrhage by reducing the occurrence or improving the outcome of delayed cerebral ischaemia. We did a trial to test whether magnesium therapy improves outcome after aneurysmal subarachnoid haemorrhage.
Methods We did this phase 3 randomised, placebo-controlled trial in eight centres in Europe and South America. We randomly assigned (with computer-generated random numbers, with permuted blocks of four, stratified by centre) patients aged 18 years or older with an aneurysmal pattern of subarachnoid haemorrhage on brain imaging who were admitted to hospital within 4 days of haemorrhage, to receive intravenous magnesium sulphate, 64 mmol/day, or placebo. We excluded patients with renal failure or bodyweight lower than 50 kg. Patients, treating physicians, and investigators assessing outcomes and analysing data were masked to the allocation. The primary outcome was poor outcome—defined as a score of 4–5 on the modified Rankin Scale—3 months after subarachnoid haemorrhage, or death. We analysed results by intention to treat. We also updated a previous meta-analysis of trials of magnesium treatment for aneurysmal subarachnoid haemorrhage. This study is registered with controlled-trials.com (ISRCTN 68742385) and the EU Clinical Trials Register (EudraCT 2006-003523-36).
Findings 1204 patients were enrolled, one of whom had his treatment allocation lost. 606 patients were assigned to the magnesium group (two lost to follow-up), 597 to the placebo (one lost to follow-up). 158 patients (26·2%) had poor outcome in the magnesium group compared with 151 (25·3%) in the placebo group (risk ratio [RR] 1·03, 95% CI 0·85–1·25). Our updated meta-analysis of seven randomised trials involving 2047 patients shows that magnesium is not superior to placebo for reduction of poor outcome after aneurysmal subarachnoid haemorrhage (RR 0·96, 95% CI 0·86–1·08).
Interpretation Intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended.
A newly published study(1) reminds us that we need to do better than just identify a raised lactate in patients with sepsis; we need to make sure it’s not increasing when they leave the ED (if we can). An incremental rise is associated with mortality.
The authors comment:
We found that the prognostic value of lactate continues to rise across a wide range of values, from 0 to 20 mmol/L…. These data suggest that grouping patients into less granular and larger groups, such as low, intermediate, and high, potentially underutilizes the prognostic value of the test. Furthermore, we did not find any value of lactate, up to a maximum value of 20 mmol/L, where mortality failed to increase with an increase in lactate concentration.
The paper does not state whether the lactate was arterial or venous, although either can be used. The Surviving Sepsis Campaign provides this comment:
In the course of the Campaign the question has been raised many times as to whether an arterial or venous lactate sample is appropriate. While there is no consensus of settled literature on this question, an elevated lactate of any variety is typically abnormal, although this may be influenced by other conditions..
This relationship between lactate trend and mortality has also been demonstrated in a study of all patients admitted to hospital (with or without sepsis), which also showed good correlation between arterial and venous lactate(2).
Always remember the good emergency physician / critical care practitioner will consider other causes of a raised lactate, particularly when things don’t add up. I invented the ‘LACTATES’ acronym to help me remember them(4), and it’s come in handy several times.
Objectives: Previous studies have confirmed the prognostic significance of lactate concentrations categorized into groups (low, intermediate, high) among emergency department (ED) patients with suspected infection. Although the relationship between lactate concentrations categorized into groups and mortality appears to be linear, the relationship between lactate as a continuous measurement and mortality is uncertain. This study sought to evaluate the association between blood lactate concentrations along an incremental continuum up to a maximum value of 20 mmol/L and mortality.
Methods: This was a retrospective cohort analysis of adult ED patients with suspected infection from a large urban ED during 2007–2010. Inclusion criteria were suspected infection evidenced by administration of antibiotics in the ED and measurement of whole blood lactate in the ED. The primary outcome was in-hospital mortality. Logistic and polynomial regression were used to model the relationship between lactate concentration and mortality.
Results: A total of 2,596 patients met inclusion criteria and were analyzed. The initial median lactate concentration was 2.1 mmol/L (interquartile range [IQR] = 1.3 to 3.3 mmol/L) and the overall mortality rate was 14.4%. In the cohort, 459 patients (17.6%) had initial lactate levels >4 mmol/L. Mortality continued to rise across the continuum of incremental elevations, from 6% for lactate <1.0 mmol/L up to 39% for lactate 19–20 mmol/L. Polynomial regression analysis showed a strong curvilinear correlation between lactate and mortality (R = 0.72, p < 0.0001).
Conclusions: In ED patients with suspected infection, we found a curvilinear relationship between incremental elevations in lactate concentration and mortality. These data support the use of lactate as a continuous variable rather than a categorical variable for prognostic purposes.
BACKGROUND: Using blood lactate monitoring for risk assessment in the critically ill patient remains controversial. Some of the discrepancy is due to uncertainty regarding the appropriate reference interval, and whether to perform a single lactate measurement as a screening method at admission to the hospital, or serial lactate measurements. Furthermore there is no consensus whether the sample should be drawn from arterial, peripheral venous, or capillary blood. The aim of this review was: 1) To examine whether blood lactate levels are predictive for in-hospital mortality in patients in the acute setting, i.e. patients assessed pre-hospitally, in the trauma centre, emergency department, or intensive care unit. 2) To examine the agreement between arterial, peripheral venous, and capillary blood lactate levels in patients in the acute setting.
METHODS: We performed a systematic search using PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL up to April 2011. 66 articles were considered potentially relevant and evaluated in full text, of these ultimately 33 articles were selected.
RESULTS AND CONCLUSION: The literature reviewed supported blood lactate monitoring as being useful for risk assessment in patients admitted acutely to hospital, and especially the trend, achieved by serial lactate sampling, is valuable in predicting in-hospital mortality. All patients with a lactate at admission above 2.5 mM should be closely monitored for signs of deterioration, but patients with even lower lactate levels should be considered for serial lactate monitoring. The correlation between lactate levels in arterial and venous blood was found to be acceptable, and venous sampling should therefore be encouraged, as the risk and inconvenience for this procedure is minimal for the patient. The relevance of lactate guided therapy has to be supported by more studies.
CONTEXT: Goal-directed resuscitation for severe sepsis and septic shock has been reported to reduce mortality when applied in the emergency department.
OBJECTIVE: To test the hypothesis of noninferiority between lactate clearance and central venous oxygen saturation (ScvO2) as goals of early sepsis resuscitation.
DESIGN, SETTING, AND PATIENTS: Multicenter randomized, noninferiority trial involving patients with severe sepsis and evidence of hypoperfusion or septic shock who were admitted to the emergency department from January 2007 to January 2009 at 1 of 3 participating US urban hospitals.
INTERVENTIONS: We randomly assigned patients to 1 of 2 resuscitation protocols. The ScvO2 group was resuscitated to normalize central venous pressure, mean arterial pressure, and ScvO2 of at least 70%; and the lactate clearance group was resuscitated to normalize central venous pressure, mean arterial pressure, and lactate clearance of at least 10%. The study protocol was continued until all goals were achieved or for up to 6 hours. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment.
MAIN OUTCOME MEASURE: The primary outcome was absolute in-hospital mortality rate; the noninferiority threshold was set at Delta equal to -10%.
RESULTS: Of the 300 patients enrolled, 150 were assigned to each group and patients were well matched by demographic, comorbidities, and physiological features. There were no differences in treatments administered during the initial 72 hours of hospitalization. Thirty-four patients (23%) in the ScvO2 group died while in the hospital (95% confidence interval [CI], 17%-30%) compared with 25 (17%; 95% CI, 11%-24%) in the lactate clearance group. This observed difference between mortality rates did not reach the predefined -10% threshold (intent-to-treat analysis: 95% CI for the 6% difference, -3% to 15%). There were no differences in treatment-related adverse events between the groups.
CONCLUSION: Among patients with septic shock who were treated to normalize central venous and mean arterial pressure, additional management to normalize lactate clearance compared with management to normalize ScvO2 did not result in significantly different in-hospital mortality.
Standard teaching in benzodiazepine (BZD) overdose is that the reversal agent flumazenil is best avoided because of the risk of seizures, particular in those patients who are BZD dependent and those who may have co-ingested proconvulsant substances such as tricyclic antidepressants.
Data from the UK’s National Poisons Information Service indicate that these principles are often flouted in the UK, and they usually get away with it, even in patients who had had seizures prior to flumazenil therapy. This will not change my practice though.
Objective Benzodiazepine (BZD) overdose (OD) continues to cause significant morbidity and mortality in the UK. Flumazenil is an effective antidote but there is a risk of seizures, particularly in those who have co-ingested tricyclic antidepressants. A study was undertaken to examine the frequency of use, safety and efficacy of flumazenil in the management of BZD OD in the UK.
Methods A 2-year retrospective cohort study was performed of all enquiries to the UK National Poisons Information Service involving BZD OD.
Results Flumazenil was administered to 80 patients in 4504 BZD-related enquiries, 68 of whom did not have ventilatory failure or had recognised contraindications to flumazenil. Factors associated with flumazenil use were increased age, severe poisoning and ventilatory failure. Co-ingestion of tricyclic antidepressants and chronic obstructive pulmonary disease did not influence flumazenil administration. Seizure frequency in patients not treated with flumazenil was 0.3%. The frequency of prior seizure in flumazenil-treated patients was 30 times higher (8.8%). Seven patients who had seizures prior to flumazenil therapy had no recurrence of their seizures. Ventilation or consciousness improved in 70% of flumazenil-treated patients. Flumazenil administration was followed by one instance each of agitation and brief seizure.
Conclusions Flumazenil is used infrequently in the management of BZD OD in the UK. It was effective and associated with a low incidence of seizure. These results compare favourably with the results of published randomised controlled trials and cohort studies, although previous studies have not reported the use of flumazenil in such a high-risk population. This study should inform the continuing review of national guidance on flumazenil therapy.
Although the worldwide emergency medicine community is split in its support for stroke thrombolysis, those who work in centres where it is provided might be interested in systems to optimise its effectiveness.
A study from the UK showed that emergency physicians can provide the majority of the service, with outcomes similar to the SITS-MOST data.
Interestingly there was only one (suspected) major intracranial haemorrhage case.
The best resource for reducing door-to-tPA time in ischaemic stroke, with heaps of related discussion, is here at EMCrit
BACKGROUND: Stroke thrombolysis is strongly supported as an effective therapy for selected cases of early stroke. The absence of 24 h stroke specialists in district general hospitals (DGHs) has led to the suggestion that regional hyper-acute stroke centres should be developed. This paper describes a cooperative model that uses the skills already present in a DGH to deliver a thrombolysis service initiated in the emergency department by the emergency physicians, and describes the outcomes of that service in comparison with the SITS-MOST trial.
METHOD: The outcomes of all stroke patients thrombolysed at Scarborough DGH from 2004 to January 2009 were reviewed. Outcome was defined using a three-part scale. Data at Scarborough DGH were compared with data from the SITS-MOST European-wide study of stroke thrombolysis.
RESULTS: Data were available for 98 of 110 patients thrombolysed during the study period. Fifty (51%) had a good outcome, seven (8%) had partial resolution of their symptoms, and 41 (42%) showed no improvement or deterioration. These outcomes were comparable to those in the European database.
CONCLUSION: Stroke thrombolysis can be effectively delivered in a non-specialist (a non-hyper-acute stroke centre) DGH in the UK. An audit of cases completed describes complications seen.
You have a patient in cardiac arrest who has had excellent resuscitation from the point of collapse, and who has treatable underlying pathology (eg. PE or STEMI). However you’re unable to get return of spontaneous circulation so you call it. Someone just died for whom the technology exists to save them. Extracorporeal life support (ECLS) supports heart and lung function by externally providing circulatory flow and gas exchange until the patient’s underlying cause of arrest is treated or recovers.
ECLS requires an extracorporeal membrane oxygenation (ECMO) circuit to be placed during the cardiac arrest resuscitation. This may sound like extreme stuff, but there have been some amazing saves with this technology, and large numbers of in-hospital and out-of-hospital arrest patients have been treated in Japan, Korea, and Taiwan. ECMO has even been commenced in the field by prehospital emergency physicians.
An inspiring EMCrit podcast with Dr Joe Bellezzo described how this technology is applied at Sharp Memorial Hospital in San Diego. Bellezzo and colleagues have now published a series of their out-of-hospital arrest cases who received ECLS initiated by emergency physicians(1).
Coming back to the Japanese, a multicentre prospective cohort study of ECLS for out-of hospital cardiac arrest (the ‘SAVE-J’ study) selected patients with VF or pulseless VT in whom no ROSC was achieved with standard resuscitative measures. Their striking results mirror other ECLS studies and were published in abstract form in November 2011(2).
To me, the overwhelming take home messages from what I’ve seen and read on this are:
1. ECLS can provide dramatic saves with neurologically intact survival in cardiac arrest cases that otherwise would be dead.
2. The critical factor for successful clinical outcomes and avoidance of wasted resources and clinical futility is case selection. The underlying cause of arrest needs to be reversible (eg. myocarditis) or treatable (eg. STEMI) and good resuscitation needs to have been in place prior to ECLS.
3. In the right hospital with the right resuscitation team, it can be done.
CONTEXT: Extracorporeal cardiopulmonary resuscitation (ECPR) refers to emergent percutaneous veno-arterial cardiopulmonary bypass to stabilize and provide temporary support of patients who suffer cardiopulmonary arrest. Initiation of ECPR by emergency physicians with meaningful long-term patient survival has not been demonstrated.
OBJECTIVE: To determine whether emergency physicians could successfully incorporate ECPR into the resuscitation of patients who present to the emergency department (ED) with cardiopulmonary collapse refractory to traditional resuscitative efforts.
DESIGN: A three-stage algorithm was developed for ED ECPR in patients meeting inclusion/exclusion criteria. We report a case series describing our experience with this algorithm over a 1-year period.
RESULTS: 42 patients presented to our ED with cardiopulmonary collapse over the 1-year study period. Of these, 18 patients met inclusion/exclusion criteria for the algorithm. 8 patients were admitted to the hospital after successful ED ECPR and 5 of those patients survived to hospital discharge neurologically intact. 10 patients were not started on bypass support because either their clinical conditions improved or resuscitative efforts were terminated.
CONCLUSION: Emergency physicians can successfully incorporate ED ECPR in the resuscitation of patients who suffer acute cardiopulmonary collapse. More studies are necessary to determine the true efficacy of this therapy.
2. Multicenter Non-Randomized Prospective Cohort Study of Extracorporeal Cardiopulmonary Resuscitation for Out-of Hospital Cardiac Arrest: Study of Advanced Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan (SAVE-J) Circulation 2011; 124: A18132 Click for abstract
Background: This study is aimed to examine the efficacy of extracorporeal cardiopulmonary resuscitation (ECPR) for patients in out-of hospital cardiac arrest (OHCA) with ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT).
Method: The design of this study is a multicenter non-randomized prospective cohort study. Hypothesis is that the outcome of OHCA with VF or pulseless VT is similar between ECPR and conventional advanced life support (ALS). During from Oct. 2008 to Dec. 2010, forty six tertiary emergency hospitals were participated in this study. Patient inclusion criteria were 1) VF or pulseless VT on scene, 2) cardiac arrest on arrival at hospital, 3) within 45 minutes from a call to an arrival of hospital, and 4) non-ROSC by conventional ALS during 15 minutes after an arrival at hospital. Exclusion criteria were 1) age: 75 yr, 2) poor activities of daily livings, 3) non-cardiac verified cardiac arrest, and 4) hypothermia. According to the inclusion criteria, ECPR was adopted for OHCA in 26 hospitals (ECPR group) and conventional ALS was planned in 20 hospitals (non-ECPR group). Both groups (Intention-to-treat) were analyzed about the proportion of patients with favorable outcome (CPC1 or 2) assessed with the Glasgow-Pittsburgh Cerebral Performance and Overall Performance Categories at 1 month by chi square test and Fisher exact probability test.
Results: One hundred and eighty patients of ECPR group and 134 patients of non-ECPR group were enrolled. There was no difference between the background of ECPR group and non-ECPR group; Average age (56.0 VS 56.9), Witnessed (72.8% VS 75.4%), Lay-rescuer CPR (49.4% VS 45.5%), Acute coronary syndrome (65.6% VS 61.4%), Minutes from collapse to emergency department (26.8 VS 30.0). The favorable outcome rate in ECPR group (12.4%, 22 patients) was statistically higher than the rate in non-ECPR group (1.6%, two patients) (p<0.001).
Conclusion: Extracorporeal cardiopulmonary resuscitation may improve the outcome of out-of hospital cardiac arrest with VF or pulseless VT without ROSC by conventional ALS during 15 minutes after an arrival at hospital.
In resuscitation situations, the securing of vascular catheters is an important but sometimes cumbersome process, particular when sutures are required for central lines or arterial lines.
Medical grade ‘superglue’ (cyanoacrylate) can be used and this has been described in the anaesthetic literature before(1). Now, further in vitro work shows the glue does not weaken the intravenous catheter and is not associated with bacterial colonisation(2).
I think this is perfect for resuscitation lines. Just last night I used this technique to secure a femoral arterial line during a cardiac arrest resuscitation. It was great not to have to faff around with sharp suture needles during CPR and the line felt very secure after just a few seconds.
Partial or complete dislodgement of intravascular catheters remains a significant problem in hospitals despite current securement methods. Cyanoacrylate tissue adhesives (TA) are used to close skin wounds as an alternative to sutures. These adhesives have high mechanical strength and can remain in situ for several days.
This study investigated in vitro use of TAs in securing intravascular catheters (IVC). We compared two adhesives for interaction with IVC material, comparing skin glues with current securement methods in terms of their ability to prevent IVC dislodgement and inhibit microbial growth. Two TAs (Dermabond, Ethicon Inc. and Histoacryl, B. Braun) and three removal agents (Remove™, paraffin and acetone) were tested for interaction with IVC material by use of tensile testing. TAs were also compared against two polyurethane (standard and bordered) dressings (Tegaderm™ 1624 and 1633, 3M Australia Pty Ltd) and an external stabilisation device (Statlock, Bard Medical, Covington) against control (unsecured IVCs) for ability to prevent pull-out of 16 G peripheral IVCs from newborn fresh porcine skin. Agar media containing pH-sensitive dye was used to assess antimicrobial properties of TAs and polyurethane dressings to inhibit growth of Staphylococcus aureus and Staphylococcus epidermidis.
Neither TA weakened the IVCs (P >0.05). Of removal agents, only acetone was associated with a significant decrease in IVC strength (P <0.05). Both TAs and Statlock significantly increased the pull-out force (P <0.01). TA was quick and easy to apply to IVCs, with no irritation or skin damage noted on removal and no bacterial colony growth under either TA.
You receive a patient resuscitated from cardiac arrest to a perfusing rhythm in your emergency department. History suggests a long ‘down time’: There was a ten minute duration of ‘no-flow’ (time from collapse to the start of resuscitation attempts).
Would this make you more likely or less likely to initiate targeted temperature management (TTM) and cool the patient to the recommended 32-34 degrees?
A recent study supports the suggestion that a longer no-flow time is associated with greater odds of survival with TTM compared with no TTM, than patients with shorter no-flow times. In other words, cooling the patient is more likely to make a difference in the ‘long down time’ patient, even though the overall survival in that group is obviously less.
Aim Mild therapeutic hypothermia has shown to improve long-time survival as well as favorable functional outcome after cardiac arrest. Animal models suggest that ischemic durations beyond 8 min results in progressively worse neurologic deficits. Based on these considerations, it would be obvious that cardiac arrest survivors would benefit most from mild therapeutic hypothermia if they have reached a complete circulatory standstill of more than 8 min.
Methods In this retrospective cohort study we included cardiac arrest survivors of 18 years of age or older suffering a witnessed out-of-hospital cardiac arrest, which remain comatose after restoration of spontaneous circulation. Data were collected from 1992 to 2010. We investigated the interaction of ‘no-flow’ time on the association between post arrest mild therapeutic hypothermia and good neurological outcome. ‘No-flow’ time was categorized into time quartiles (0, 1–2, 3–8, >8 min).
Results One thousand-two-hundred patients were analyzed. Hypothermia was induced in 598 patients. In spite of showing a statistically significant improvement in favorable neurologic outcome in all patients treated with mild therapeutic hypothermia (odds ratio [OR]: 1.49; 95% confidence interval [CI]: 1.14–1.93) this effect varies with ‘no-flow’ time. The effect is significant in patients with ‘no-flow’ times of more than 2 min (OR: 2.72; CI: 1.35–5.48) with the maximum benefit in those with ‘no-flow’ times beyond 8 min (OR: 6.15; CI: 2.23–16.99).
Conclusion The beneficial effect of mild therapeutic hypothermia increases with cumulative time of complete circulatory standstill in patients with witnessed out-of-hospital cardiac arrest.
Full text access is only available to New England Journal subscribers, but I’ve summarised some of the interesting bits in a short quiz you can take to test your knowledge. Just 13 True/False questions.