Tag Archives: outcome

All Updates, ICU, Resus, Trauma

CRASH-2 and head injury

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The overall effect of the antifibrinolytic drug tranexamic acid on outcome from major trauma was assessed in the CRASH-2 trial, reported here and here. Its effect on a nested cohort of 270 patients from the trial who had traumatic brain injury has now been published1.
Previous evaluation in nontraumatic subarachnoid haemorrhage patients showed tranexamic acid to be associated with cerebral ischaemia, whereas in CRASH-2 (in which a lower dose of tranexamic acid was used) there was a trend to fewer ischaemic lesions as well as smaller haematoma growth and decreased mortality. None of these outcomes were statistically significant so further research is warranted.
An accompanying editorial2 states:

…the CRASH-2 study also justifies a re-evaluation of the possible benefit of low dose short term TXA in patients with other types of intracranial haemorrhage. Many patients with aneurysmal subarachnoid haemorrhage still have to wait for one or two days before the aneurysm is occluded. In addition, at least 30% of patients with spontaneous intracerebral haemorrhage experience substantial haematoma growth in the first 24 hours after the onset of the haemorrhage. As well as the CRASH-2 trial we therefore need new trials investigating short course low dose TXA in patients with aneurysmal subarachnoid haemorrhage and intracerebral haemorrhage.

It looks like considerable enthusiasm for this drug will be around for a while. I look forward to more outcome data, particularly in regard to this challenging group of patients with traumatic and non-traumatic intracranial bleeding.


OBJECTIVE: To assess the effect of tranexamic acid (which reduces bleeding in surgical patients and reduces mortality due to bleeding in trauma patients) on intracranial haemorrhage in patients with traumatic brain injury.

METHODS: A nested, randomised, placebo controlled trial. All investigators were masked to treatment allocation. All analyses were by intention to treat. Patients 270 adult trauma patients with, or at risk of, significant extracranial bleeding within 8 hours of injury, who also had traumatic brain injury.

INTERVENTIONS: Patients randomly allocated to tranexamic acid (loading dose 1 g over 10 minutes, then infusion of 1 g over 8 hours) or matching placebo.

MAIN OUTCOME MEASURES: Intracranial haemorrhage growth (measured by computed tomography) between hospital admission and then 24-48 hours later, with adjustment for Glasgow coma score, age, time from injury to the scans, and initial haemorrhage volume.

RESULTS: Of the 133 patients allocated to tranexamic acid and 137 allocated to placebo, 123 (92%) and 126 (92%) respectively provided information on the primary outcome. All patients provided information on clinical outcomes. The mean total haemorrhage growth was 5.9 ml (SD 26.8) and 8.1 mL (SD 29.2) in the tranexamic acid and placebo groups respectively (adjusted difference -3.8 mL (95% confidence interval -11.5 to 3.9)). New focal cerebral ischaemic lesions occurred in 6 (5%) patients in the tranexamic acid group versus 12 (9%) in the placebo group (adjusted odds ratio 0.51 (95% confidence interval 0.18 to 1.44)). There were 14 (11%) deaths in the tranexamic acid group and 24 (18%) in the placebo group (adjusted odds ratio 0.47 (0.21 to 1.04)).

CONCLUSIONS: This trial shows that neither moderate benefits nor moderate harmful effects of tranexamic acid in patients with traumatic brain injury can be excluded. However, the analysis provides grounds for further clinical trials evaluating the effect of tranexamic acid in this population

1. Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study)
BMJ. 2011 Jul 1;343:d379 (free text available)
2. Tranexamic acid for traumatic brain injury
BMJ. 2011 Jul 1;343:d3958

All Updates, ICU, Resus

Crike rate 1 in 500 in Scottish ED

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A review of over 2500 intubation attempts in the emergency department1, (of which 1671 were rapid sequence intubation attempts) revealed five cricothyroidotomies, giving a crike rate of 0.2% which is much lower than in some other ED based registries. In four patients, predictors of difficult airway were identified before the endotracheal intubation attempt, and formal preparation for rescue surgical airway was performed. Three of the surgical airways were performed by emergency medicine trainees, one by an emergency medicine specialist and one by an ear, nose and throat specialist. There was a 100% success rate for placement of all surgical airways on the first attempt.

Four surgical airways were done in trauma patients: laryngeal fracture, facial burns, Le Fort II facial fracture and penetrating neck injury.
This study is of interest to UK emergency physicians who may be interested in Edinburgh Royal Infirmary’s collaborative approach to emergency airway management by the Departments of Emergency Medicine, Anaesthesia and Critical Care.
It is not possible to tell from this paper whether there were patients in whom surgical airway was indicated but not performed, and therefore in my view the ostensibly ‘good’ low rate of 0.2% should be viewed with interest rather than awe. Having said that, this figure is more in keeping with my own experience and expectation from UK/Australasian practice; it has been highlighted in the UK EM literature before2, including by myself3, that in our patient group good training and supervision should result in lower surgical airway rates than the ~1% often quoted.


OBJECTIVES: To determine the frequency of and primary indication for surgical airway during emergency department intubation.

METHODS: Prospectively collected data from all intubations performed in the emergency department from January 1999 to July 2007 were analysed to ascertain the frequency of surgical airway access. Original data were collected on a structured proforma, entered into a regional database and analysed. Patient records were then reviewed to determine the primary indication for a surgical airway.

RESULTS: Emergency department intubation was undertaken in 2524 patients. Of these, only five patients (0.2%) required a surgical airway. The most common indication for a surgical airway was trauma in four of the five patients. Two patients had attempted rapid sequence induction before surgical airway. Two patients had gaseous inductions and one patient received no drugs. In all five patients, surgical airway was performed secondary to failed endotracheal intubation attempt(s) and was never the primary technique used.

CONCLUSION: In our emergency department, surgical airway is an uncommon procedure. The rate of 0.2% is significantly lower than rates quoted in other studies. The most common indication for surgical airway was severe facial or neck trauma. Our emergency department has a joint protocol for emergency intubation agreed by the Departments of Emergency Medicine, Anaesthesia and Critical Care at the Edinburgh Royal Infirmary. We believe that the low surgical airway rate is secondary to this collaborative approach. The identified low rate of emergency department surgical airway has implications for training and maintenance of skills for emergency medicine trainees and physicians.

1. Surgical airway in emergency department intubation
Eur J Emerg Med. 2011 Jun;18(3):168-71
2. Rapid sequence induction in the emergency department: a strategy for failure.
Emerg Med J. 2002 Mar;19(2):109-13
3. RSI by non-anaesthetists in the UK – lower incidence of cricothyrotomy than in the US
EMJ e-letters 2002; 3 April

Acute Med, All Updates, ICU, PHARM, Resus

How much oxygen after ROSC?

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I reported a previous JAMA publication demonstrating an association between hyperoxia and mortality in patients resuscitated post-cardiac arrest. The same authors have published furthur data to better define the relationship between supranormal oxygen tension and outcome in postresuscitation patients. They hypothesised that a linear dose-dependent relationship would be present in the association between supranormal oxygen tension and in-hospital mortality.

Background– Laboratory and recent clinical data suggest that hyperoxemia after resuscitation from cardiac arrest is harmful; however, it remains unclear if the risk of adverse outcome is a threshold effect at a specific supranormal oxygen tension, or is a dose-dependent association. We aimed to define the relationship between supranormal oxygen tension and outcome in postresuscitation patients.

Methods and Results– This was a multicenter cohort study using the Project IMPACT database (intensive care units at 120 US hospitals). Inclusion criteria were age >17 years, nontrauma, cardiopulmonary resuscitation preceding intensive care unit arrival, and postresuscitation arterial blood gas obtained. We excluded patients with hypoxia or severe oxygenation impairment. We defined the exposure by the highest partial pressure of arterial oxygen (PaO(2)) over the first 24 hours in the ICU. The primary outcome measure was in-hospital mortality. We tested the association between PaO(2) (continuous variable) and mortality using multivariable logistic regression adjusted for patient-oriented covariates and potential hospital effects. Of 4459 patients, 54% died. The median postresuscitation PaO(2) was 231 (interquartile range 149 to 349) mm Hg. Over ascending ranges of oxygen tension, we found significant linear trends of increasing in-hospital mortality and decreasing survival as functionally independent. On multivariable analysis, a 100 mm Hg increase in PaO(2) was associated with a 24% increase in mortality risk (odds ratio 1.24 [95% confidence interval 1.18 to 1.31]. We observed no evidence supporting a single threshold for harm from supranormal oxygen tension.

Conclusion– In this large sample of postresuscitation patients, we found a dose-dependent association between supranormal oxygen tension and risk of in-hospital death.

Relationship Between Supranormal Oxygen Tension and Outcome After Resuscitation From Cardiac Arrest
Circulation. 2011 Jun 14;123(23):2717-2722
Australasian investigators provided the following critique of the original JAMA study:

Unfortunately, these investigators used only the first set of arterial blood gases in the ICU to assess oxygenation, excluded close to 30% of patients because of lack of arterial blood gas data and did not adjust for standard illness severity scores. Their conclusion that hyperoxia is a robust predictor of mortality in patients after resuscitation form cardiac arrest was therefore potentially affected by selection bias and by insufficient adjustment for major confounders. Thus, their results are of uncertain significance and require confirmation.
They undertook their own study of 12,108 patients:

INTRODUCTION: Hyperoxia has recently been reported as an independent risk factor for mortality in patients resuscitated from cardiac arrest. We examined the independent relationship between hyperoxia and outcomes in such patients.
METHODS: We divided patients resuscitated from nontraumatic cardiac arrest from 125 intensive care units (ICUs) into three groups according to worst PaO2 level or alveolar-arterial O2 gradient in the first 24 hours after admission. We defined ‘hyperoxia’ as PaO2 of 300 mmHg or greater, ‘hypoxia/poor O2 transfer’ as either PaO2 < 60 mmHg or ratio of PaO2 to fraction of inspired oxygen (FiO2 ) < 300, ‘normoxia’ as any value between hypoxia and hyperoxia and ‘isolated hypoxemia’ as PaO2 < 60 mmHg regardless of FiO2. Mortality at hospital discharge was the main outcome measure.

RESULTS: Of 12,108 total patients, 1,285 (10.6%) had hyperoxia, 8,904 (73.5%) had hypoxia/poor O2 transfer, 1,919 (15.9%) had normoxia and 1,168 (9.7%) had isolated hypoxemia (PaO2 < 60 mmHg). The hyperoxia group had higher mortality (754 (59%) of 1,285 patients; 95% confidence interval (95% CI), 56% to 61%) than the normoxia group (911 (47%) of 1,919 patients; 95% CI, 45% to 50%) with a proportional difference of 11% (95% CI, 8% to 15%), but not higher than the hypoxia group (5,303 (60%) of 8,904 patients; 95% CI, 59% to 61%). In a multivariable model controlling for some potential confounders, including illness severity, hyperoxia had an odds ratio for hospital death of 1.2 (95% CI, 1.1 to 1.6). However, once we applied Cox proportional hazards modelling of survival, sensitivity analyses using deciles of hypoxemia, time period matching and hyperoxia defined as PaO2 > 400 mmHg, hyperoxia had no independent association with mortality. Importantly, after adjustment for FiO2 and the relevant covariates, PaO2 was no longer predictive of hospital mortality (P = 0.21).

CONCLUSIONS: Among patients admitted to the ICU after cardiac arrest, hyperoxia did not have a robust or consistently reproducible association with mortality. We urge caution in implementing policies of deliberate decreases in FiO2 in these patients.

Arterial hyperoxia and in-hospital mortality after resuscitation from cardiac arrest.
Crit Care. 2011 Mar 8;15(2):R90. [Epub ahead of print]
Open Access Full Text
What’s the best approach in the light of these differing results? My approach is to avoid hypoxia, since that’s probably bad, and to actively avoid overoxygenating as part of my general neuroprotection checklist in a post-cardiac arrest patient. It would seem prudent to follow the recommendations of ILCOR, summarised by the European Resuscitation Council guidelines as:

Recognition of the potential harm caused by hyperoxaemia after ROSC is achieved: once ROSC has been established and the oxygen saturation of arterial blood (SaO2) can be monitored reliably (by pulse oximetry and/or arterial blood gas analysis), inspired oxygen is titrated to achieve a SaO2 of 94–98%

All Updates, ICU, PHARM, Resus, Trauma

How about pre-hospital tranexamic acid?

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The CRASH 2 trial showed improved outcomes in trauma from the administration of the antifibrinolytic drug tranexamic acid. A further analysis of the data has shown that benefit was only seen in CRASH-2 when tranexamic acid was administered within 3 hours of injury1.
An accompanying editorial2 makes the following interesting points:

  • Acute traumatic coagulopathy is a hyperacute process in which systemic fibrinolysis releases D-dimers that are detectable within 30 min of injury.
  • Those severely injured patients who develop acute coagulopathy are much more likely to die and to die early.
  • Once fully activated, fibrinolysis has been shown to continue unabated until endogenous antifibrinolytic elements are restored.
  • The earlier that tranexamic acid is administered, the more likely it might be to prevent full activation of fibrinolysis.
  • Hospital massive transfusion protocols incorporate fresh frozen plasma that contains all the endogenous antifibrinolytic elements in plasma and so the place for tranexamic acid in high income countries with such protocols is unclear.
  • The best place for tranexamic acid in developed trauma systems might actually be in the prehospital environment, where trauma bypass policies have extended prehospital times and the administration of plasma is uncommon and often impractical.

BACKGROUND: The aim of the CRASH-2 trial was to assess the effects of early administration of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage. Tranexamic acid significantly reduced all-cause mortality. Because tranexamic acid is thought to exert its effect through inhibition of fibrinolysis, we undertook exploratory analyses of its effect on death due to bleeding.

METHODS: The CRASH-2 trial was undertaken in 274 hospitals in 40 countries. 20,211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min followed by infusion of 1 g over 8 h) or placebo. Patients were randomly assigned by selection of the lowest numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Both participants and study staff (site investigators and trial coordinating centre staff ) were masked to treatment allocation. We examined the effect of tranexamic acid on death due to bleeding according to time to treatment, severity of haemorrhage as assessed by systolic blood pressure, Glasgow coma score (GCS), and type of injury. All analyses were by intention to treat. The trial is registered as ISRCTN86750102, ClinicalTrials.gov NCT00375258, and South African Clinical Trial Register/Department of Health DOH-27-0607-1919.

FINDINGS: 10,096 patients were allocated to tranexamic acid and 10,115 to placebo, of whom 10,060 and 10,067, respectively, were analysed. 1063 deaths (35%) were due to bleeding. We recorded strong evidence that the effect of tranexamic acid on death due to bleeding varied according to the time from injury to treatment (test for interaction p<0.0001). Early treatment (≤1 h from injury) significantly reduced the risk of death due to bleeding (198/3747 [5.3%] events in tranexamic acid group vs 286/3704 [7.7%] in placebo group; relative risk [RR] 0.68, 95% CI 0.57-0.82; p<0.0001). Treatment given between 1 and 3 h also reduced the risk of death due to bleeding (147/3037 [4.8%] vs 184/2996 [6.1%]; RR 0.79, 0.64-0.97; p=0.03). Treatment given after 3 h seemed to increase the risk of death due to bleeding (144/3272 [4.4%] vs 103/3362 [3.1%]; RR 1.44, 1.12-1.84; p=0.004). We recorded no evidence that the effect of tranexamic acid on death due to bleeding varied by systolic blood pressure, Glasgow coma score, or type of injury.

INTERPRETATION: Tranexamic acid should be given as early as possible to bleeding trauma patients. For trauma patients admitted late after injury, tranexamic acid is less effective and could be harmful.

1. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial
Lancet. 2011 Mar 26;377(9771):1096-101
2. Tranexamic acid for trauma
Lancet. 2011 Mar 26;377(9771):1052-4

Acute Med, All Updates, ICU, Resus

Dexamethasone for community acquired pneumonia

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Another Dutch study has examined steroids for community acquired pneumonia, this time with the primary outcome measure being hospital length of stay, which was reduced by one day on the steroid group. Compare this study with a previous negative study of prednisolone for pneumonia.

BACKGROUND: Whether addition of corticosteroids to antibiotic treatment benefits patients with community-acquired pneumonia who are not in intensive care units is unclear. We aimed to assess effect of addition of dexamethasone on length of stay in this group, which might result in earlier resolution of pneumonia through dampening of systemic inflammation.

METHODS: In our double-blind, placebo-controlled trial, we randomly assigned adults aged 18 years or older with confirmed community-acquired pneumonia who presented to emergency departments of two teaching hospitals in the Netherlands to receive intravenous dexamethasone (5 mg once a day) or placebo for 4 days from admission. Patients were ineligible if they were immunocompromised, needed immediate transfer to an intensive-care unit, or were already receiving corticosteroids or immunosuppressive drugs. We randomly allocated patients on a one-to-one basis to treatment groups with a computerised randomisation allocation sequence in blocks of 20. The primary outcome was length of hospital stay in all enrolled patients. This study is registered with ClinicalTrials.gov, number NCT00471640.

FINDINGS: Between November, 2007, and September, 2010, we enrolled 304 patients and randomly allocated 153 to the placebo group and 151 to the dexamethasone group. 143 (47%) of 304 enrolled patients had pneumonia of pneumonia severity index class 4-5 (79 [52%] patients in the dexamethasone group and 64 [42%] controls). Median length of stay was 6·5 days (IQR 5·0-9·0) in the dexamethasone group compared with 7·5 days (5·3-11·5) in the placebo group (95% CI of difference in medians 0-2 days; p=0·0480). In-hospital mortality and severe adverse events were infrequent and rates did not differ between groups, although 67 (44%) of 151 patients in the dexamethasone group had hyperglycaemia compared with 35 (23%) of 153 controls (p<0·0001).

INTERPRETATION: Dexamethasone can reduce length of hospital stay when added to antibiotic treatment in non-immunocompromised patients with community-acquired pneumonia.

Dexamethasone and length of hospital stay in patients with community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial
Lancet. 2011 Jun 11;377(9782):2023-30

Acute Med, All Updates, Guidelines, ICU, Kids, Resus, Trauma, Ultrasound

Central lines in coagulopathic patients

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If a patient needs a central line, he/she needs one. Often low platelets or a deranged coagulation profile are cited as reasons for omitting or delaying the procedure, but this is not based on evidence of increased complications. A recent Best Evidence Topic Review concludes:

“…insertion of CVC lines do not require correction of haemostatic abnormalities prior to intervention. Rates of haemorrhage are low in patients with elevated PT, APTT or low thrombocyte count and appear to be closely related to the level of experience of the physician … rather than the defects of haemostasis. “

Links to the abstracts of a couple of relevant articles reviewed are included below.
Central line insertion in deranged clotting
Emerg Med J. 2011 Jun;28(6):536-7 Full text
Low levels of prothrombin time (INR) and platelets do not increase the risk of significant bleeding when placing central venous catheters.
Med Klin (Munich). 2009 May 15;104(5):331-5
US-guided placement of central vein catheters in patients with disorders of hemostasis
Eur J Radiol. 2008 Feb;65(2):253-6

All Updates, ICU

Neurologic complications in infective endocarditis

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More than half of patients admitted to ICU with left-sided infective endocarditis developed neurologic complications

OBJECTIVE: To describe the clinical spectrum of infective endocarditis in critically ill patients and assess the impact of neurologic complications on outcomes.
DESIGN: Prospective multicenter observational study conducted from April 2007 to October 2008.
SETTING: Thirty-three intensive care units in 23 university-affiliated and 10 general French hospitals.
PATIENTS: Two hundred twenty-five patients with definite IE were studied. Factors associated with neurologic complications and predictors of 3-month mortality were identified by logistic regression analysis. Functional outcomes of patients with neurologic complications were evaluated with the modified Rankin Scale.
MEASUREMENTS AND MAIN RESULTS: Among 198 patients with definite left-sided infective endocarditis, 108 (55%) experienced at least one neurologic complication. These complications were ischemic stroke (n = 79), cerebral hemorrhage (n = 53), meningitis or meningeal reaction (n = 41), brain abscess (n = 14), and mycotic aneurysm (n = 10). Factors independently associated with neurologic complications were (subhazard ratio [95% confidence interval]): Staphylococcus aureus infective endocarditis (1.45 [1.02-2.05]), mitral valve infective endocarditis (1.54 [1.07-2.21]), and nonneurologic embolic events (1.51 [1.09-2.09]). In contrast, health care-associated infective endocarditis had a protective effect (0.46 [0.27-0.77]). Multivariate analysis identified three variables associated with 3-month mortality (odds ratio [95% confidence interval]): neurologic failure, as defined as a Glasgow Coma Scale <10 (7.41 [2.89-18.96]), S. aureus infective endocarditis (3.26 [1.53-6.94]), and severe comorbidities before admission as defined as a Charlson score >2 (3.16 [1.47-6.77]). Among the 106 patients with neurologic complications assessed at follow-up (3.9 [3-8.5] months), 31 (29%) had a modified Rankin Scale score ≤3 (ability to walk without assistance), nine (9%) a modified Rankin Scale score of 4 or 5 (severe disability), and 66 (62%) a modified Rankin Scale score of 6 (death).
CONCLUSIONS: Neurologic events are the most frequent complications in infective endocarditis patients requiring intensive care unit admission. They contribute to a severe prognosis, leaving less than one-third of patients alive with functional independence. Neurologic failure at intensive care unit admission represents a major determinant of mortality regardless of the underlying neurologic complication.

Neurologic complications and outcomes of infective endocarditis in critically ill patients: The ENDOcardite en REAnimation prospective multicenter study
Crit Care Med. 2011 Jun;39(6):1474-1481

Acute Med, All Updates, Guidelines, ICU, Resus

ACEP policy on PE

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The American College of Emergency Physicians has revised its 2003 clinical policy on pulmonary embolism.


 
Among the areas considered is the the role of thrombolytic medication. The policy provides the following recommendations to this question:

What are the indications for thrombolytic therapy in patients with PE?
Level B recommendations
Administer thrombolytic therapy in hemodynamically unstable patients with confirmed PE for whom the benefits of treatment outweigh the risks of life-threatening bleeding complications.*
*In centers with the capability for surgical or mechanical thrombectomy, procedural intervention may be used as an alternative therapy.
Level C recommendations
(1) Consider thrombolytic therapy in hemodynamically unstable patients with a high clinical suspicion for PE for whom the diagnosis of PE cannot be confirmed in a timely manner.
(2) At this time, there is insufficient evidence to make any recommendations regarding use of thrombolytics in any subgroup of hemodynamically stable patients. Thrombolytics have been demonstrated to result in faster improvements in right ventricular function and pulmonary perfusion, but these benefits have not translated to improvements in mortality.

The document contains a detailed appraisal of the literature to date on benefits and harms from thrombolysis. Of interest is the Pulmonary Embolism Severity Index (PESI) – a scoring system that appears to reliably predict mortality and thus has the potential to assist physicians in making risk-benefit decisions when considering administration of thrombolytics. The full text of the policy, which covers far more than just thrombolysis, can be found by following the link below.
Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Suspected Pulmonary Embolism
Annals of Emergency Medicine 2011 June 57(6):628-652 – Free Full Text

All Updates, ICU, Resus, Trauma

Steroids for trauma

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A French study on adult patients intubated for multiple trauma assessed the effect of a one week course of stress-dose hydrocortisone therapy against placebo on the incidence of hospital-acquired pneumonia. Multiple trauma was defined as having 2 or more traumatic injuries and an injury severity score higher than 15. The primary outcome measure was hospital-acquired pneumonia, defined by robust criteria and requiring positive lower respiratory tract microbiology. The study was not powered to detect a difference in mortality. The authors conclude that a stress dose of hydrocortisone for 7 days is associated with a reduction in the rate of hospital-acquired pneumonia at day 28 together with a decreased requirement for mechanical ventilation and length of ICU stay in trauma patients.
An accompanying editorial, highlighting the contrast in these results with those of other steroid-studies such as the CRASH trial, which used higher doses of steroid for a shorter period, cautions:
“the overall evidence suggests that further study with a larger sample size is needed to better define the safety profile and risk of mortality in this patient population.”

Context The role of stress-dose hydrocortisone in the management of trauma patients is currently unknown.

Objective To test the efficacy of hydrocortisone therapy in trauma patients.

Design, Setting, and Patients Multicenter, randomized, double-blind, placebo-controlled HYPOLYTE (Hydrocortisone Polytraumatise) study. From November 2006 to August 2009, 150 patients with severe trauma were included in 7 intensive care units in France.

Intervention Patients were randomly assigned to a continuous intravenous infusion of either hydrocortisone (200 mg/d for 5 days, followed by 100 mg on day 6 and 50 mg on day 7) or placebo. The treatment was stopped if patients had an appropriate adrenal response.

Main Outcome Measure Hospital-acquired pneumonia within 28 days. Secondary outcomes included the duration of mechanical ventilation, hyponatremia, and death.

Results One patient withdrew consent. An intention-to-treat (ITT) analysis included the 149 patients, a modified ITT analysis included 113 patients with corticosteroid insufficiency. In the ITT analysis, 26 of 73 patients (35.6%) treated with hydrocortisone and 39 of 76 patients (51.3%) receiving placebo developed hospital-acquired pneumonia by day 28 (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.30-0.83; P = .007). In the modified ITT analysis, 20 of 56 patients (35.7%) in the hydrocortisone group and 31 of 57 patients (54.4%) in the placebo group developed hospital-acquired pneumonia by day 28 (HR, 0.47; 95% CI, 0.25-0.86; P = .01). Mechanical ventilation–free days increased with hydrocortisone by 4 days (95% CI, 2-7; P = .001) in the ITT analysis and 6 days (95% CI, 2-11; P < .001) in the modified ITT analysis. Hyponatremia was observed in 7 of 76 (9.2%) in the placebo group vs none in the hydrocortisone group (absolute difference, −9%; 95% CI, −16% to −3%; P = .01). Four of 76 patients (5.3%) in the placebo group and 6 of 73 (8.2%) in the hydrocortisone group died (absolute difference, 3%; 95% CI, −5% to 11%; P = .44).

Conclusion In intubated trauma patients, the use of an intravenous stress-dose of hydrocortisone, compared with placebo, resulted in a decreased risk of hospital-acquired pneumonia.

Hydrocortisone therapy for patients with multiple trauma: the randomized controlled HYPOLYTE study
JAMA. 2011 Mar 23;305(12):1201-9

Acute Med, All Updates, Resus

Erythropoietin for STEMI

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In STEMI patients, intravenous erythropoietin within 4 hours of PCI did not reduce infarct size and was associated with higher rates of adverse cardiovascular events

Context Acute ST-segment elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality. In experimental models of MI, erythropoietin reduces infarct size and improves left ventricular (LV) function.

Objective To evaluate the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with STEMI.

Design, Setting, and Patients A prospective, randomized, double-blind, placebo-controlled trial with a dose-escalation safety phase and a single dose (60 000 U of epoetin alfa) efficacy phase; the Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction (REVEAL) trial was conducted at 28 US sites between October 2006 and February 2010, and included 222 patients with STEMI who underwent successful percutaneous coronary intervention (PCI) as a primary or rescue reperfusion strategy.

Intervention Participants were randomly assigned to treatment with intravenous epoetin alfa or matching saline placebo administered within 4 hours of reperfusion.

Main Outcome Measure Infarct size, expressed as percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging performed 2 to 6 days after study medication administration (first CMR) and again 12 ± 2 weeks later (second CMR).

Results In the efficacy cohort, the infarct size did not differ between groups on either the first CMR scan (n = 136; 15.8% LV mass [95% confidence interval {CI}, 13.3-18.2% LV mass] for the epoetin alfa group vs 15.0% LV mass [95% CI, 12.6-17.3% LV mass] for the placebo group; P = .67) or on the second CMR scan (n = 124; 10.6% LV mass [95% CI, 8.4-12.8% LV mass] vs 10.4% LV mass [95% CI, 8.5-12.3% LV mass], respectively; P = .89). In a prespecified analysis of patients aged 70 years or older (n = 21), the mean infarct size within the first week (first CMR) was larger in the epoetin alfa group (19.9% LV mass; 95% CI, 14.0-25.7% LV mass) than in the placebo group (11.7% LV mass; 95% CI, 7.2-16.1% LV mass) (P = .03). In the safety cohort, of the 125 patients who received epoetin alfa, the composite outcome of death, MI, stroke, or stent thrombosis occurred in 5 (4.0%; 95% CI, 1.31%-9.09%) but in none of the 97 who received placebo (P = .04).

Conclusions In patients with STEMI who had successful reperfusion with primary or rescue PCI, a single intravenous bolus of epoetin alfa within 4 hours of PCI did not reduce infarct size and was associated with higher rates of adverse cardiovascular events. Subgroup analyses raised concerns about an increase in infarct size among older patients.

Intravenous Erythropoietin in Patients With ST-Segment Elevation Myocardial Infarction
JAMA. 2011 May 11;305(18):1863-72