Tag Archives: outcome

Post-arrest hypothermia in children did not improve outcome

Many clinicians extrapolate adult research findings to paediatric patients because there’s no alternative, and until now we’ve had to do that with post-cardiac arrest therapeutic hypothermia after paediatric cardiac arrest.

However the THAPCA trial in the New England Journal of Medicine now provides child-specific data.

It was a multicentre trial in the US which included children between 2 days and 18 years of age, who had had an out-of-hospital cardiac arrest and remained comatose after return of circulation. They were randomised to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C) within 6 hours after the return of circulation.

Therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit with respect to survival with good functional outcome at 1 year, and survival at 12 months did not differ significantly between the treatment groups.

These findings are similar to the adult TTM trial, although there are some interesting differences. In the paediatric study, the duration of temperature control was longer (120 hrs vs 36 hrs in the adult study), respiratory conditions were the predominant cause of paediatric cardiac arrest (72%), and there were only 8% shockable rhythms in the paediatric patients, compared with 80% in the adult study.

The full text is available here.

Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children
N Engl J Med. 2015 Apr 25

Background: Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited.

Methods: We conducted this trial of two targeted temperature interventions at 38 children’s hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest.

Results: A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality.

Conclusions: In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year.

Esmolol for refractory VF

Already well publicised on social media, the team at Hennepin County published a retrospective comparison between patients with refractory VF who received esmolol with those who did not(1). The results are impressive and I look forward to further studies on this.

I work in an ED in a hospital with no cath lab and no access to extracorporeal life support, limiting our options for patients who remain in shockable rhythms despite ACLS interventions. We now have esmolol available in our resus room. You might want to keep it in your list of options for ACLS-refractory VF, which might also include double sequential external defibrillation(2) and even stellate ganglion block.

The dose of esmolol used was: loading dose 500 mcg/kg, followed by infusions of 0, 50, or 100 mcg/kg/min

An important point to note in the esmolol study is that almost all patients received high-quality mechanical CPR with the combined use of an impedence threshold device to augment venous return and cardiac output. The authors “speculate that this additional hemodynamic support may be essential given the hypotensive effects of esmolol.”

1. Use of esmolol after failure of standard cardiopulmonary resuscitation to treat patients with refractory ventricular fibrillation
Resuscitation. 2014 Oct;85(10):1337-41

INTRODUCTION: We compare the outcomes for patients who received esmolol to those who did not receive esmolol during refractory ventricular fibrillation (RVF) in the emergency department (ED).

METHODS: A retrospective investigation in an urban academic ED of patients between January 2011 and January 2014 of patients with out-of-hospital or ED cardiac arrest (CA) with an initial rhythm of ventricular fibrillation (VF) or ventricular tachycardia (VT) who received at least three defibrillation attempts, 300mg of amiodarone, and 3mg of adrenaline, and who remained in CA upon ED arrival. Patients who received esmolol during CA were compared to those who did not.

RESULTS: 90 patients had CA with an initial rhythm of VF or VT; 65 patients were excluded, leaving 25 for analysis. Six patients received esmolol during cardiac arrest, and nineteen did not. All patients had ventricular dysrhythmias refractory to many defibrillation attempts, including defibrillation after administration of standard ACLS medications. Most received high doses of adrenaline, amiodarone, and sodium bicarbonate. Comparing the patients that received esmolol to those that did not: 67% and 42% had temporary return of spontaneous circulation (ROSC); 67% and 32% had sustained ROSC; 66% and 32% survived to intensive care unit admission; 50% and 16% survived to hospital discharge; and 50% and 11% survived to discharge with a favorable neurologic outcome, respectively.

CONCLUSION: Beta-blockade should be considered in patients with RVF in the ED prior to cessation of resuscitative efforts.

2. Double Sequential External Defibrillation in Out-of-Hospital Refractory Ventricular Fibrillation: A Report of Ten Cases.
Prehosp Emerg Care. 2015 January-March;19(1):126-130

Background. Ventricular fibrillation (VF) is considered the out-of-hospital cardiac arrest (OOHCA) rhythm with the highest likelihood of neurologically intact survival. Unfortunately, there are occasions when VF does not respond to standard defibrillatory shocks. Current American Heart Association (AHA) guidelines acknowledge that the data are insufficient in determining the optimal pad placement, waveform, or energy level that produce the best conversion rates from OOHCA with VF.

Objective. To describe a technique of double sequential external defibrillation (DSED) for cases of refractory VF (RVF) during OOHCA resuscitation.

Methods. A retrospective case series was performed in an urban/suburban emergency medical services (EMS) system with advanced life support care and a population of 900,000. Included were all adult OOHCAs having RVF during resuscitation efforts by EMS providers. RVF was defined as persistent VF following at least 5 unsuccessful single shocks, epinephrine administration, and a dose of antiarrhythmic medication. Once the patient was in RVF, EMS personnel applied a second set of pads and utilized a second defibrillator for single defibrillation with the new monitor/pad placement. If VF continued, EMS personnel then utilized the original and second monitor/defibrillator charged to maximum energy, and shocks were delivered from both machines simultaneously. Data were collected from electronic dispatch and patient care reports for descriptive analysis.

Results. From 01/07/2008 to 12/31/2010, a total of 10 patients were treated with DSED. The median age was 76.5 (IQR: 65-82), with median resuscitation time of 51minutes (IQR: 45-62). The median number of single shocks was 6.5 (IQR: 6-11), with a median of 2 (IQR: 1-3) DSED shocks delivered. VF broke after DSED in 7 cases (70%). Only 3 patients (30%) had ROSC in the field, and none survived to discharge.

Conclusion. This case series demonstrates that DSED may be a feasible technique as part of an aggressive treatment plan for RVF in the out-of-hospital setting. In this series, RVF was terminated 70% of the time, but no patient survived to discharge. Further research is needed to better understand the characteristics of and treatment strategies for RVF.

Blunt traumatic arrest in kids

Traumatic cardiac arrest outcomes are not great, but they’re not so bad that resuscitation is futile – a subject I’ve ranted about before.

The largest study on blunt traumatic arrest in children to date has been published, showing that 340 / 7766 kids without signs of life in the field survived to hospital discharge. Neurological status at discharge was not documented. However, this represents 4.4%, or in other words for every 22 blunt traumatically arrested children who underwent prehospital resuscitation, one survived to discharge. The authors describe this survival as ‘dismal’. It’s not great, but my take on it is that survival is possible and in most cases resuscitation should be attempted.

The authors state:

Based on these data, EMS providers should not be discouraged from resuscitating blunt pediatric trauma patients found in the field with no signs of life

While the major focus should be on injury prevention, it is worthwhile considering whether more advanced resuscitation in the field could be provided to further increase the number of neurologically intact survivors.

Survival of pediatric blunt trauma patients presenting with no signs of life in the field
J Trauma Acute Care Surg. 2014 Sep;77(3):422-6

BACKGROUND: Prehospital traumatic cardiopulmonary arrest is associated with dismal prognosis, and patients rarely survive to hospital discharge. Recently established guidelines do not apply to the pediatric population because of paucity of data. The study objective was to determine the survival of pediatric patients presenting in the field with no signs of life after blunt trauma.

METHODS: We conducted a retrospective analysis of the National Trauma Data Bank research data set (2002-2010). All patients 18 years and younger with blunt traumatic injuries were identified (DRG International Classification of Diseases-9th Rev. codes 800-869). No signs of life (SOL) was defined on physical examination findings and included the following: pulse, 0; respiratory rate, 0; systolic blood pressure, 0; and no evidence of neurologic activity. These same criteria were reassessed on arrival at the emergency department (ED). Furthermore, we examined patients presenting to the ED who underwent resuscitative thoracotomy (Current Procedural Terminology code 34.02). Our primary outcome was survival to discharge from the hospital.

RESULTS: There were a total of 3,115,597 pediatric patients who were found in the field after experiencing blunt trauma. Of those, 7,766 (0.25%) had no SOL. Seventy percent of the patients with no SOL in the field were male. Survival to hospital discharge of all patients presenting with no SOL was 4.4% (n = 340). Twenty-five percent of the patients in the field with no SOL were successfully resuscitated in the field and regained SOL by the time they arrived to the ED (n = 1,913). Of those patients who regained SOL, 13.8% (n = 265) survived to hospital discharge. For patients in the field with no SOL, survival to discharge was significantly higher in patients who did not receive a resuscitative thoracotomy than in those who did.

CONCLUSION: Survival of pediatric blunt trauma patients in the field without SOL is dismal. Resuscitative thoracotomy poses a heightened risk of blood-borne pathogen exposure to involved health care workers and is associated with a significantly lower survival rate.

Breaking with tradition in paediatric RSI

‘Traditional’ rapid sequence induction of anaesthesia is often described with inclusion of cricoid pressure and the strict omission of any artifical ventilation between paralytic drug administration and insertion of the tracheal tube. These measures are aimed at preventing pulmonary aspiration of gastric contents although there is no convincing evidence base to support that. However it is known that cricoid pressure can worsen laryngoscopic view and can occlude the paediatric airway. We also know that children desaturate quickly after the onset of apnoea, and although apnoeic diffusion oxygenation via nasal cannula can prevent or delay that, in some cases it may be preferable to bag-mask ventilate the patient while awaiting full muscle relaxation for laryngoscopy.

A Swiss study looked at 1001 children undergoing RSI for non-cardiac surgery. They used a ‘controlled rapid sequence induction and intubation (cRSII)’ approach for children assumed to have full stomachs. This procedure resembled RSI the way it is currently done in many modern critical care settings, including the retrieval service I work for:

  • No cricoid pressure
  • Ketamine for induction if haemodynamically unstable
  • A non-depolarising neuromuscular blocker rather than succinylcholine
  • No cricoid pressure
  • Gentle facemask ventilation to maintain oxygenation until intubation conditions achieved
  • Intubation with a cuffed tracheal tube
  • Still no cricoid pressure

The authors comment:

The main finding was that cRSII demonstrated a considerably lower incidence of oxygen desaturation and consecutive hemodynamic adverse events during anesthesia induction than shown by a previous study on classic RSII in children. Furthermore, there was no incidence of pulmonary aspiration during induction, laryngoscopy, and further course of anesthesia.

Looks like more dogma has been lysed, and this study supports the current trajectory away from traditional teaching towards an approach more suitable for critically ill patients.

Controlled rapid sequence induction and intubation – an analysis of 1001 children
Paediatr Anaesth. 2013 Aug;23(8):734-40

BACKGROUND: Classic rapid sequence induction puts pediatric patients at risk of cardiorespiratory deterioration and traumatic intubation due to their reduced apnea tolerance and related shortened intubation time. A ‘controlled’ rapid sequence induction and intubation technique (cRSII) with gentle facemask ventilation prior to intubation may be a safer and more appropriate approach in pediatric patients. The aim of this study was to analyze the benefits and complications of cRSII in a large cohort.

METHODS: Retrospective cohort analysis of all patients undergoing cRSII according to a standardized institutional protocol between 2007 and 2011 in a tertiary pediatric hospital. By means of an electronic patient data management system, vital sign data were reviewed for cardiorespiratory parameters, intubation conditions, general adverse respiratory events, and general anesthesia parameters.

RESULTS: A total of 1001 patients with cRSII were analyzed. Moderate hypoxemia (SpO2 80-89%) during cRSII occurred in 0.5% (n = 5) and severe hypoxemia (SpO2 <80%) in 0.3% of patients (n = 3). None of these patients developed bradycardia or hypotension. Overall, one single gastric regurgitation was observed (0.1%), but no pulmonary aspiration could be detected. Intubation was documented as ‘difficult’ in two patients with expected (0.2%) and in three patients with unexpected difficult intubation (0.3%). The further course of anesthesia as well as respiratory conditions after extubation did not reveal evidence of ‘silent aspiration’ during cRSII.

CONCLUSION: Controlled RSII with gentle facemask ventilation prior to intubation supports stable cardiorespiratory conditions for securing the airway in children with an expected or suspected full stomach. Pulmonary aspiration does not seem to be significantly increased.

Etomidate – there is always a downside

By Norwegian intensivist/anaesthetist/HEMS Physician Dr Per Bredmose.

[Warning – Rant level: Viking]

Etomidate has for a long time been known in some countries as the “drug of choice” for RSI in unstable/fragile patients. This is due to the fact that induction with etomidate is fairly cardiovascularly stable. However, there is a down side: a subsequent suppression of adrenal function. This was initially discovered after etomidate was used for sedation infusions on ICU.

It has for a long time been debated whether this is a side effect with clinical implications after a single dose induction… and yes it has.

A recent Japanese study demonstrates this(1). This is a large propensity based study. Now, propensity based statistics are pretty complex to explain. In short, it is an advanced method to strengthen the statistics when comparing groups in non-cross over studies.

In this study 2616 patients receiving etomidate for induction and a volatile agent for maintenance are included.
This showed an increased OR for 30-days mortality with a factor of 2.5 and 1.5 times greater chance for a major cardiovascular event in hospital. Interestingly enough, there were no significant differences in either perioperative vasopressor use or infections complications during hospital stay.

What does this mean?
In my mind and experience, it strengthens the fact that there is no wonder drug. And also that there seems to be a reason for why etomidate is de-registered in many countries.
Also, it tells me that for a safe prehospital RSI we need physicians capable of clinical judgment and “decision making” to tailor an (any) induction agent to the specific individual patient. In my mind, there is no room for an etomidate-only (dose / weight) induction protocol!

1. Komatsu R, You J, Mascha EJ, Sessler DI, Kasuya Y, Turan A.
Anesthetic induction with etomidate, rather than propofol, is associated with increased 30-day mortality and cardiovascular morbidity after noncardiac surgery.
Anesth Analg. 2013 Dec;117(6):1329-37

Double balloon pump fail

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?
Lancet 2013;382:1616-7

Hyperchloraemia and mortality

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.

Isolated LAFB and outcome

A small study followed up an older cohort of patients with isolated left anterior fascicular block on their ECG (isolated left axis deviation), without clinically manifest cardiovascular disease.

Learn about LAFB at Life In The Fast Lane

LAFB was associated with an increased risk of atrial fibrillation, heart failure and death. LAFB is caused by conduction tissue fibrosis, and is a marker of other left heart fibrosis. The patients did not go on to develop left bundle branch block, and only 2 of 39 required pacing in 10 years, suggesting these outcomes were not due to progression of conduction disease.

Long-term Outcomes of Left Anterior Fascicular Block in the Absence of Overt Cardiovascular Disease
JAMA. 2013 Apr 17;309(15):1587-8

Blood products in trauma & survivor bias

Esky-label.001The observation that patients with haemorrhagic trauma in military and civilian settings do better if they receive coagulation factors and platelets is yet to be replicated in a randomised trial. It has been suggested that the effect may in part be a consequence of survivor bias – ie. that if a patient lives long enough to received some thawed fresh frozen plasma, then they were already more likely to be a survivor and therefore more survivors will be represented in the ‘FFP’ groups vs a ‘no-FFP’ comparison group.

An attempt to eliminate survivor bias was made in the PROMMTT study, which documented the timing of transfusions during active resuscitation and patient outcomes in adult trauma patients who received a transfusion of at least 1 unit of RBCs within 6 hours of admission.

Increased ratios of plasma:RBCs and platelets:RBCs were independently associated with decreased 6-hour mortality, when haemorrhagic death predominated. In the first 6 hours, patients with ratios less than 1:2 were 3 to 4 times more likely to die than patients with ratios of 1:1 or higher.

A prospective trial is underway to identify the optimal ratio of blood products, in the PROPPR study, in which 1:1:1 ratio of plasma:platelets:RBC will be compared with 1:1:2.

The Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) Study
Arch Surg. 2012 Oct 15:1-10

Objective: To relate in-hospital mortality to early transfusion of plasma and/or platelets and to time-varying plasma:red blood cell (RBC) and platelet:RBC ratios.

Design: Prospective cohort study documenting the timing of transfusions during active resuscitation and patient outcomes. Data were analyzed using time-dependent proportional hazards models.

Setting: Ten US level I trauma centers.

Patients: Adult trauma patients surviving for 30 minutes after admission who received a transfusion of at least 1 unit of RBCs within 6 hours of admission (n = 1245, the original study group) and at least 3 total units (of RBCs, plasma, or platelets) within 24 hours (n = 905, the analysis group).

Main Outcome Measure: In-hospital mortality.

Results: Plasma:RBC and platelet:RBC ratios were not constant during the first 24 hours (P < .001 for both). In a multivariable time-dependent Cox model, increased ratios of plasma:RBCs (adjusted hazard ratio = 0.31; 95% CI, 0.16-0.58) and platelets:RBCs (adjusted hazard ratio = 0.55; 95% CI, 0.31-0.98) were independently associated with decreased 6-hour mortality, when hemorrhagic death predominated. In the first 6 hours, patients with ratios less than 1:2 were 3 to 4 times more likely to die than patients with ratios of 1:1 or higher. After 24 hours, plasma and platelet ratios were unassociated with mortality, when competing risks from nonhemorrhagic causes prevailed.

Conclusions: Higher plasma and platelet ratios early in resuscitation were associated with decreased mortality in patients who received transfusions of at least 3 units of blood products during the first 24 hours after admission. Among survivors at 24 hours, the subsequent risk of death by day 30 was not associated with plasma or platelet ratios.

Stroke thrombolysis outcomes from registry

Data from a large national stroke registry are reported to show that in patients who received tPA, outcomes were worse the later it was given. From a registry of over a million patients, the study group included 58353 patients from 1395 sites treated after emergency department arrival with IV tPA within 4.5 hours of symptom onset. Reported odds ratios were small but statistically significant in this large sample size. There was a 4.9% rate of intracranial haemorrhage.

As there is no comparison with patients who did not receive tPA, one cannot conclude from this study that tPA is either beneficial or harmful. It may however be used as an argument that if you’re working in a centre where the patients are going to get the tPA, it’s advisable not to delay it.

Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke
JAMA. 2013 Jun 19;309(23):2480-8

IMPORTANCE: Randomized clinical trials suggest the benefit of intravenous tissue-type plasminogen activator (tPA) in acute ischemic stroke is time dependent. However, modest sample sizes have limited characterization of the extent to which onset to treatment (OTT) time influences outcome; and the generalizability of findings to clinical practice is uncertain.

OBJECTIVE: To evaluate the degree to which OTT time is associated with outcome among patients with acute ischemic stroke treated with intraveneous tPA.

DESIGN, SETTING, AND PATIENTS: Data were analyzed from 58,353 patients with acute ischemic stroke treated with tPA within 4.5 hours of symptom onset in 1395 hospitals participating in the Get With The Guidelines-Stroke Program, April 2003 to March 2012.

MAIN OUTCOMES AND MEASURES: Relationship between OTT time and in-hospital mortality, symptomatic intracranial hemorrhage, ambulatory status at discharge, and discharge destination.

RESULTS: Among the 58,353 tPA-treated patients, median age was 72 years, 50.3% were women, median OTT time was 144 minutes (interquartile range, 115-170), 9.3% (5404) had OTT time of 0 to 90 minutes, 77.2% (45,029) had OTT time of 91 to 180 minutes, and 13.6% (7920) had OTT time of 181 to 270 minutes. Median pretreatment National Institutes of Health Stroke Scale documented in 87.7% of patients was 11 (interquartile range, 6-17). Patient factors most strongly associated with shorter OTT included greater stroke severity (odds ratio [OR], 2.8; 95% CI, 2.5-3.1 per 5-point increase), arrival by ambulance (OR, 5.9; 95% CI, 4.5-7.3), and arrival during regular hours (OR, 4.6; 95% CI, 3.8-5.4). Overall, there were 5142 (8.8%) in-hospital deaths, 2873 (4.9%) patients had intracranial hemorrhage, 19,491 (33.4%) patients achieved independent ambulation at hospital discharge, and 22,541 (38.6%) patients were discharged to home. Faster OTT, in 15-minute increments, was associated with reduced in-hospital mortality (OR, 0.96; 95% CI, 0.95-0.98; P < .001), reduced symptomatic intracranial hemorrhage (OR, 0.96; 95% CI, 0.95-0.98; P < .001), increased achievement of independent ambulation at discharge (OR, 1.04; 95% CI, 1.03-1.05; P < .001), and increased discharge to home (OR, 1.03; 95% CI, 1.02-1.04; P < .001).

CONCLUSIONS AND RELEVANCE: In a registry representing US clinical practice, earlier thrombolytic treatment was associated with reduced mortality and symptomatic intracranial hemorrhage, and higher rates of independent ambulation at discharge and discharge to home following acute ischemic stroke. These findings support intensive efforts to accelerate hospital presentation and thrombolytic treatment in patients with stroke.