A paper published today represents to me what’s great about science.
I am impressed with those investigators who had the wherewithall to subject previous therapeutic hypothermia studies to skeptical scrutiny and then design and conduct a robust multicentre trial to answer the question.
One of the criticisms of the original two studies was that those patients who were not actively cooled did not have their temperature tightly controlled, and therefore some were allowed to become hypERthermic, which is bad for brains.
This latest study showed no difference in survival or neurological outcome after cardiac arrest between target temperatures of 33°C and 36°C.
So controlling the temperature after cardiac arrest is still important, but cooling down to the recommended range of 32-4°C is not.
Read the full study at the NEJM site.
Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest
NEJM November 17, 2013 Full text
BACKGROUND Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever.
METHODS In an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale.
RESULTS In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar.
CONCLUSIONS In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C.
Two recent trials question the ongoing use of intra-aortic balloon pumps: in patients with acute myocardial infarction with cardiogenic shock undergoing revascularisation(1), and patients with poor left ventricular function undergoing coronary artery bypass surgery(2).
Editorialists Krischan D Sjauw and Jan J Piek from the Netherlands make the following commentary(3) in reference to one of the studies:
Although the results of IABP-SHOCK II question the usefulness of IABP therapy in cardiogenic shock, there still might be an indication for initial stabilisation of severely compromised patients, especially in centres without facilities for early revascularisation, as an adjunct to thrombolytic therapy, or to allow transport to specialised tertiary centres.
So retrieval specialists like me may still be up in the night transferring patients with balloon pumps, but these studies suggest this should be restricted to those with cardiogenic shock pending corrective therapy (eg. revascularisation for AMI or surgery for acute mitral valvular dysfunction). Unless the ECMO team gets to them first, of course.
1. Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABP-SHOCK II): final 12 month results of a randomised, open-label trial
The Lancet, Volume 382, Issue 9905, Pages 1638 – 1645
BACKGROUND: In current international guidelines the recommendation for intra-aortic balloon pump (IABP) use has been downgraded in cardiogenic shock complicating acute myocardial infarction on the basis of registry data. In the largest randomised trial (IABP-SHOCK II), IABP support did not reduce 30 day mortality compared with control. However, previous trials in cardiogenic shock showed a mortality benefit only at extended follow-up. The present analysis therefore reports 6 and 12 month results.
METHODS: The IABP-SHOCK II trial was a randomised, open-label, multicentre trial. Patients with cardiogenic shock complicating acute myocardial infarction who were undergoing early revascularisation and optimum medical therapy were randomly assigned (1:1) to IABP versus control via a central web-based system. The primary efficacy endpoint was 30 day all-cause mortality, but 6 and 12 month follow-up was done in addition to quality-of-life assessment for all survivors with the Euroqol-5D questionnaire. A masked central committee adjudicated clinical outcomes. Patients and investigators were not masked to treatment allocation. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00491036.
FINDINGS: Between June 16, 2009, and March 3, 2012, 600 patients were assigned to IABP (n=301) or control (n=299). Of 595 patients completing 12 month follow-up, 155 (52%) of 299 patients in the IABP group and 152 (51%) of 296 patients in the control group had died (relative risk [RR] 1·01, 95% CI 0·86-1·18, p=0·91). There were no significant differences in reinfarction (RR 2·60, 95% CI 0·95-7·10, p=0·05), recurrent revascularisation (0·91, 0·58-1·41, p=0·77), or stroke (1·50, 0·25-8·84, p=1·00). For survivors, quality-of-life measures including mobility, self-care, usual activities, pain or discomfort, and anxiety or depression did not differ significantly between study groups.
INTERPRETATION: In patients undergoing early revascularisation for myocardial infarction complicated by cardiogenic shock, IABP did not reduce 12 month all-cause mortality.
2. A Randomized Controlled Trial of Preoperative Intra-Aortic Balloon Pump in Coronary Patients With Poor Left Ventricular Function Undergoing Coronary Artery Bypass Surgery
Crit Care Med. 2013 Nov;41(11):2476-83
BACKGROUND: Preoperative intra-aortic balloon pump use in high-risk patients undergoing surgical coronary revascularization is still a matter of debate. The objective of this study is to determine whether the preoperative use of an intra-aortic balloon pump improves the outcome after coronary operations in high-risk patients.
DESIGN: Single-center prospective randomized controlled trial.
SETTING: Tertiary cardiac surgery center, research hospital.
PATIENTS: One hundred ten subjects undergoing coronary operations, with a poor left ventricular ejection fraction (< 35%) and no hemodynamic instability.
Patients randomized to receive preincision intra-aortic balloon pump or no intervention.
MEASUREMENTS AND MAIN RESULTS: The primary outcome measurement was postoperative major morbidity rate, defined as one of prolonged mechanical ventilation, stroke, acute kidney injury, surgical revision, mediastinitis, and operative mortality. There was no difference in major morbidity rate (40% in intra-aortic balloon pump group and 31% in control group; odds ratio, 1.49 [95% CI, 0.68-3.33]). No differences were observed for cardiac index before and after the operation; at the arrival in the ICU, patients in the intra-aortic balloon pump group had a significantly (p = 0.01) lower mean systemic arterial pressure (80.1 ± 15.1 mm Hg) versus control group patients (89.2 ± 17.9 mm Hg). Fewer patients in the intra-aortic balloon pump group (24%) than those in the control group (44%) required dopamine infusion (p = 0.043).
CONCLUSIONS: This study demonstrates that in patients undergoing nonemergent coronary operations, with a stable hemodynamic profile and a left ventricular ejection fraction less than 35%, the preincision insertion of intra-aortic balloon pump does not result in a better outcome. Given the possible complications of intra-aortic balloon pump insertion, and the additional cost of the procedure, this approach is not justified.
3. Is the intra-aortic balloon pump leaking?
Counterintuitive as it sounds, this is pretty cool. I blogged about these guys before when they published their findings on microcirculatory flow in septic patients given beta blockers.
It’s a small study – 77 patients with septic shock and a heart rate of 95/min or higher requiring high-dose norepinephrine to maintain a mean arterial pressure of at least 65 mm Hg were randomised to receive a continuous infusion of esmolol titrated to maintain heart rate between 80/min and 94/min for their ICU stay. 77 patients received standard treatment. It should be noted the primary outcome (target heart rate) was not a patient-oriented endpoint. Interestingly though, there were no increased adverse events in the beta blocker group, which demonstrated improved left ventricular stroke work, lower lactate levels, decreased noradrenaline and fluid requirements, improved oxygenation, and a lower mortality.
Caution is appropriate here though: this study was a small, single-centre open-label trial. It will be very interesting to see if these effects are reproduced and whether they will ultimately translate to meaningful outcome benefits.
Read more about the study at the PulmCCM site.
There is also a great critical appraisal of the study at Emergency Medicine Literature of Note/a>.
Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial
JAMA. 2013 Oct 23;310(16):1683-91
IMPORTANCE: β-Blocker therapy may control heart rate and attenuate the deleterious effects of β-adrenergic receptor stimulation in septic shock. However, β-Blockers are not traditionally used for this condition and may worsen cardiovascular decompensation related through negative inotropic and hypotensive effects.
OBJECTIVE: To investigate the effect of the short-acting β-blocker esmolol in patients with severe septic shock.
DESIGN, SETTING, AND PATIENTS: Open-label, randomized phase 2 study, conducted in a university hospital intensive care unit (ICU) between November 2010 and July 2012, involving patients in septic shock with a heart rate of 95/min or higher requiring high-dose norepinephrine to maintain a mean arterial pressure of 65 mm Hg or higher.
INTERVENTIONS: We randomly assigned 77 patients to receive a continuous infusion of esmolol titrated to maintain heart rate between 80/min and 94/min for their ICU stay and 77 patients to standard treatment.
MAIN OUTCOMES AND MEASURES: Our primary outcome was a reduction in heart rate below the predefined threshold of 95/min and to maintain heart rate between 80/min and 94/min by esmolol treatment over a 96-hour period. Secondary outcomes included hemodynamic and organ function measures; norepinephrine dosages at 24, 48, 72, and 96 hours; and adverse events and mortality occurring within 28 days after randomization.
RESULTS: Targeted heart rates were achieved in all patients in the esmolol group compared with those in the control group. The median AUC for heart rate during the first 96 hours was -28/min (IQR, -37 to -21) for the esmolol group vs -6/min (95% CI, -14 to 0) for the control group with a mean reduction of 18/min (P < .001). For stroke volume index, the median AUC for esmolol was 4 mL/m2 (IQR, -1 to 10) vs 1 mL/m2 for the control group (IQR, -3 to 5; P = .02), whereas the left ventricular stroke work index for esmolol was 3 mL/m2 (IQR, 0 to 8) vs 1 mL/m2 for the control group (IQR, -2 to 5; P = .03). For arterial lactatemia, median AUC for esmolol was -0.1 mmol/L (IQR, -0.6 to 0.2) vs 0.1 mmol/L for the control group (IQR, -0.3 for 0.6; P = .007); for norepinephrine, -0.11 μg/kg/min (IQR, -0.46 to 0.02) for the esmolol group vs -0.01 μg/kg/min (IQR, -0.2 to 0.44) for the control group (P = .003). Fluid requirements were reduced in the esmolol group: median AUC was 3975 mL/24 h (IQR, 3663 to 4200) vs 4425 mL/24 h(IQR, 4038 to 4775) for the control group (P < .001). We found no clinically relevant differences between groups in other cardiopulmonary variables nor in rescue therapy requirements. Twenty-eight day mortality was 49.4% in the esmolol group vs 80.5% in the control group (adjusted hazard ratio, 0.39; 95% CI, 0.26 to 0.59; P < .001).
CONCLUSIONS AND RELEVANCE: For patients in septic shock, open-label use of esmolol vs standard care was associated with reductions in heart rates to achieve target levels, without increased adverse events. The observed improvement in mortality and other secondary clinical outcomes warrants further investigation.
It’s nice to have big randomised trials to guide critical care practice. The age-old crystalloid/colloid debate (is that still going?) has fueled a multicentre and multinational study in 2857 patients with hypovolaemic shock on intensive care units. Patients were classified as having sepsis, trauma, or other causes of hypovolaemic shock.
In the crystalloids group, allowed treatments included isotonic or hypertonic saline and any buffered solutions. In the colloids group, gelatins, albumin from 4-25%, dextrans, and hydroxyethyl starches were permitted.
The primary outcome of 28 day mortality was no different between groups. The study had an open-label design and recruitment took place over nine years.
This finding – no clinical benefit from colloids in critically ill patients – is in keeping with other major ICU trials of colloid therapy: Saline versus Albumin Fluid Evaluation (SAFE), Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP), Scandinavian Starch for Severe Sepsis/Septic Shock (6S), and the Crystalloid versus Hydroxyethyl Starch Trial (CHEST).
Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial
JAMA. 2013 Nov 6;310(17):1809-17
IMPORTANCE: Evidence supporting the choice of intravenous colloid vs crystalloid solutions for management of hypovolemic shock remains unclear.
OBJECTIVE: To test whether use of colloids compared with crystalloids for fluid resuscitation alters mortality in patients admitted to the intensive care unit (ICU) with hypovolemic shock.
DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized clinical trial stratified by case mix (sepsis, trauma, or hypovolemic shock without sepsis or trauma). Therapy in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) trial was open label but outcome assessment was blinded to treatment assignment. Recruitment began in February 2003 and ended in August 2012 of 2857 sequential ICU patients treated at 57 ICUs in France, Belgium, North Africa, and Canada; follow-up ended in November 2012.
INTERVENTIONS: Colloids (n = 1414; gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) or crystalloids (n = 1443; isotonic or hypertonic saline or Ringer lactate solution) for all fluid interventions other than fluid maintenance throughout the ICU stay.
MAIN OUTCOMES AND MEASURES: The primary outcome was death within 28 days. Secondary outcomes included 90-day mortality; and days alive and not receiving renal replacement therapy, mechanical ventilation, or vasopressor therapy.
RESULTS: Within 28 days, there were 359 deaths (25.4%) in colloids group vs 390 deaths (27.0%) in crystalloids group (relative risk [RR], 0.96 [95% CI, 0.88 to 1.04]; P = .26). Within 90 days, there were 434 deaths (30.7%) in colloids group vs 493 deaths (34.2%) in crystalloids group (RR, 0.92 [95% CI, 0.86 to 0.99]; P = .03). Renal replacement therapy was used in 156 (11.0%) in colloids group vs 181 (12.5%) in crystalloids group (RR, 0.93 [95% CI, 0.83 to 1.03]; P = .19). There were more days alive without mechanical ventilation in the colloids group vs the crystalloids group by 7 days (mean: 2.1 vs 1.8 days, respectively; mean difference, 0.30 [95% CI, 0.09 to 0.48] days; P = .01) and by 28 days (mean: 14.6 vs 13.5 days; mean difference, 1.10 [95% CI, 0.14 to 2.06] days; P = .01) and alive without vasopressor therapy by 7 days (mean: 5.0 vs 4.7 days; mean difference, 0.30 [95% CI, -0.03 to 0.50] days; P = .04) and by 28 days (mean: 16.2 vs 15.2 days; mean difference, 1.04 [95% CI, -0.04 to 2.10] days; P = .03).
CONCLUSIONS AND RELEVANCE: Among ICU patients with hypovolemia, the use of colloids vs crystalloids did not result in a significant difference in 28-day mortality. Although 90-day mortality was lower among patients receiving colloids, this finding should be considered exploratory and requires further study before reaching conclusions about efficacy.
Patients with refractory (>30 mins) cardiac arrest underwent prehospital cannulation for extracorporeal life support in a French feasibility study. A physician-paramedic team responded by car in Paris to cardiac arrest cases that met inclusion criteria. Mechanical CPR devices (Autopulse or LUCAS) were applied during cannulation. Femoral venoarterial ECMO was instituted using a Maquet Cardiohelp system. Blood products and inotropes, echocardiography, and hypothermia were included in the prehospital management package.
Seven patients were treated, with a mean age of 42 (+/- SD of 16, no median given). ECLS was started an average 57 min (±21) after the onset of ACLS. One patient survived to discharge neurologically intact. Two brain dead patients became organ donors. The survivor had hypertrophic cardiomyopathy with refractory ventricular ﬁbrillation.
Safety and feasibility of prehospital extra corporeal life support implementation by non-surgeons for out-of-hospital refractory cardiac arrest
Resuscitation. 2013 Nov;84(11):1525-9
BACKGROUND: Extra corporeal life support (ECLS) has been recently introduced in the treatment of refractory cardiac arrest (CA). Several studies have assessed the use of ECLS in refractory CA once the patients reach hospital. The time between CA and the implementation of ECLS is a major prognostic factor for survival. The main predictive factor for survival is ECLS access time. Pre hospital ECLS implementation could reduce access time. We therefore decided to assess the feasibility and safety of prehospital ECLS implementation (PH-ECLS) in a pilot study.
METHODS AND RESULTS: From January 2011 to January 2012, PH-ECLS implementation for refractory CA was performed in 7 patients by a PH-ECLS team including emergency and/or intensivist physicians and paramedics. Patients were included prospectively and consecutively if the following criteria were met: they had a witnessed CA; CPR was initiated within the first 5min of CA and/or there were signs of life during CPR; an PH-ECLS team was available and absence of severe comorbidities. ECLS flow was established in all patients. ECLS was started 22min (±6) after the incision, and 57min (±21) after the onset of advanced cardiovascular life support (ACLS). In one patient, ECLS was stopped for 10min due to an accidental decannulation. One patient survived without sequelae. Three patients developed brain death.
CONCLUSIONS: This pilot study suggests that PH-ECLS performed by non-surgeons is safe and feasible. Further studies are needed to confirm the time saved by this strategy and its potential effect on survival.
Here’s something to add to the pile of data cautioning us to think before we acidify patients with saline. A study in Anesthesia and Analgesia using propensity matching provides retrospective evidence that patients who developed hyperchloremia after noncardiac surgery had worse outcomes.
For more information on why saline isn’t ‘normal’ see: What’s with all the chloride? An assault on salt
Hyperchloremia after noncardiac surgery is independently associated with increased morbidity and mortality: a propensity-matched cohort study
Anesth Analg. 2013 Aug;117(2):412-21
BACKGROUND: The use of normal saline is associated with hyperchloremic metabolic acidosis. In this study, we sought to determine the incidence of acute postoperative hyperchloremia (serum chloride >110 mEq/L) and whether this electrolyte disturbance is associated with an increase in length of hospital stay, morbidity, or 30-day postoperative mortality.
METHODS: Data were retrospectively collected on consecutive adult patients (>18 years of age) who underwent inpatient, noncardiac, nontransplant surgery between January 1, 2003 and December 31, 2008. The impact of postoperative hyperchloremia on patient morbidity and length of hospital stay was examined using propensity-matched and logistic multivariable analysis.
RESULTS: The dataset consisted of 22,851 surgical patients with normal preoperative serum chloride concentration and renal function. Acute postoperative hyperchloremia (serum chloride >110 mmol/L) is quite common, with an incidence of 22%. Patients were propensity-matched based on their likelihood to develop acute postoperative hyperchloremia. Of the 4955 patients with hyperchloremia after surgery, 4266 (85%) patients were matched to patients who had normal serum chloride levels after surgery. These 2 groups were well balanced with respect to all variables collected. The hyperchloremic group was at increased risk of mortality at 30 days postoperatively (3.0% vs 1.9%; odds ratio = 1.58; 95% confidence interval, 1.25-1.98) (relative risk 1.6 or risk increase of 1.1%) and had a longer hospital stay (7.0 days [interquartile range 4.1-12.3] compared with 6.3 [interquartile range 4.0-11.3]) than patients with normal postoperative serum chloride levels. Patients with postoperative hyperchloremia were more likely to have postoperative renal dysfunction. Using all preoperative variables and measured outcome variables in a logistic regression analysis, hyperchloremia remained an independent predictor of 30-day mortality with an odds ratio of 2.05 (95% confidence interval, 1.62-2.59).
CONCLUSION: This retrospective cohort trial demonstrates an association between hyperchloremia and poor postoperative outcome. Additional studies are required to demonstrate a causal relationship between these variables.
A reminder that the closing date for abstracts for the SMACC Gold conference is Friday 22nd November 2013.
Why should I care?
Remember this may well end up being the best critical care / emergency medicine / prehospital & retrieval medicine conference in the universe.
Submitting an abstract is good for you. As well contributing to education and the world medical knowledge base, you’ll get an extra line in the ‘academic’ section of your CV, which will make you at least appear smart.
What can you submit? This doesn’t have to be ground breaking research. Case reports, audits, topic reviews, and even ideas have been accepted as conference abstracts in the past (you’re building a picture of my CV now).
This means you still have time to come up with something, and submit it. What’s the worst thing that can happen? It’s like dating – as long as your self esteem can cope with rejection, you’re better off asking than not asking.
Submit here. You might get a yes, adding instant turgidity to your CV.
Remember also that it’s MUCH harder for your colleagues and/or employer to stop you going if you’re presenting a poster or oral session.
I have no financial interest in the SMACC Gold conference