High Frequency Oscillation Trial Results

Here’s a heads up on a major evidence-based medicine event in critical care: the results of two long awaited randomised controlled trials assessing high-frequency oscillation (HFOV) in Acute Respiratory Distress Syndrome (ARDS) have both been published, and the full text is available from the New England Journal of Medicine at the links below.

In summary, the Oscillation for Acute Respiratory Distress Syndrome Treated Early (OSCILLATE)(1) and the Oscillation in ARDS (OSCAR)(2) trials showed no improvement in in-hospital death or 30 day mortality, respectively. OSCILLATE was terminated early on the basis of a strong signal for increased mortality with HFOV.

An editorial discusses some of the reasons why these outcomes were seen, which include among other factors the possibility that they were related to increased requirements for sedation, paralysis, and vasoactive drugs in the HFOV patients that were not offset by improvements in oxygenation and lung recruitment.

1. High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome
NEJM 22 Jan 2013

BACKGROUND Previous trials suggesting that high-frequency oscillatory ventilation (HFOV) reduced mortality among adults with the acute respiratory distress syndrome (ARDS) were limited by the use of outdated comparator ventilation strategies and small sample sizes

METHODS In a multicenter, randomized, controlled trial conducted at 39 intensive care units in five countries, we randomly assigned adults with new-onset, moderate-to-severe ARDS to HFOV targeting lung recruitment or to a control ventilation strategy targeting lung recruitment with the use of low tidal volumes and high positive end-expiratory pressure. The primary outcome was the rate of in-hospital death from any cause.

RESULTS On the recommendation of the data monitoring committee, we stopped the trial after 548 of a planned 1200 patients had undergone randomization. The two study groups were well matched at baseline. The HFOV group underwent HFOV for a median of 3 days (interquartile range, 2 to 8); in addition, 34 of 273 patients (12%) in the control group received HFOV for refractory hypoxemia. In-hospital mortality was 47% in the HFOV group, as compared with 35% in the control group (relative risk of death with HFOV, 1.33; 95% confidence interval, 1.09 to 1.64; P=0.005). This finding was independent of baseline abnormalities in oxygenation or respiratory compliance. Patients in the HFOV group received higher doses of midazolam than did patients in the control group (199 mg per day [interquartile range, 100 to 382] vs. 141 mg per day [interquartile range, 68 to 240], P<0.001), and more patients in the HFOV group than in the control group received neuromuscular blockers (83% vs. 68%, P<0.001). In addition, more patients in the HFOV group received vasoactive drugs (91% vs. 84%, P=0.01) and received them for a longer period than did patients in the control group (5 days vs. 3 days, P=0.01).

CONCLUSIONS In adults with moderate-to-severe ARDS, early application of HFOV, as compared with a ventilation strategy of low tidal volume and high positive end-expiratory pressure, does not reduce, and may increase, in-hospital mortality. (Funded by the Canadian Institutes of Health Research; Current Controlled Trials numbers, ISRCTN42992782 and ISRCTN87124254, and ClinicalTrials.gov numbers, NCT00474656 and NCT01506401.)

2. High-Frequency Oscillation for Acute Respiratory Distress Syndrome
NEJM 22 Jan 2013

BACKGROUND Patients with the acute respiratory distress syndrome (ARDS) require mechanical ventilation to maintain arterial oxygenation, but this treatment may produce secondary lung injury. High-frequency oscillatory ventilation (HFOV) may reduce this secondary damage.

METHODS In a multicenter study, we randomly assigned adults requiring mechanical ventilation for ARDS to undergo either HFOV with a Novalung R100 ventilator (Metran) or usual ventilatory care. All the patients had a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) of 200 mm Hg (26.7 kPa) or less and an expected duration of ventilation of at least 2 days. The primary outcome was all-cause mortality 30 days after randomization

RESULTS There was no significant between-group difference in the primary outcome, which occurred in 166 of 398 patients (41.7%) in the HFOV group and 163 of 397 patients (41.1%) in the conventional-ventilation group (P=0.85 by the chi-square test). After adjustment for study center, sex, score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, and the initial PaO2:FiO2 ratio, the odds ratio for survival in the conventional-ventilation group was 1.03 (95% confidence interval, 0.75 to 1.40; P=0.87 by logistic regression).

CONCLUSIONS The use of HFOV had no significant effect on 30-day mortality in patients undergoing mechanical ventilation for ARDS. (Funded by the National Institute for Health Research Health Technology Assessment Programme; OSCAR Current Controlled Trials number, ISRCTN10416500.

Advanced airways and worse outcomes in cardiac arrest

A new study demonstrates an association between advanced prehospital airway management and worse clinical outcomes in patients with cardiac arrest. Done in Japan, the numbers of patients included are staggering: this nationwide population-based cohort study included 658 829 adult patients. They found that CPR with advanced airway management (use of tracheal tubes and even supraglottic airways) was a significant predictor of poor neurological outcome compared with conventional bag-valve-mask ventilation.

Association of Prehospital Advanced Airway Management With Neurologic Outcome and Survival in Patients With Out-of-Hospital Cardiac Arrest
JAMA 2013;309(3):257-66

Importance It is unclear whether advanced airway management such as endotracheal intubation or use of supraglottic airway devices in the prehospital setting improves outcomes following out-of-hospital cardiac arrest (OHCA) compared with conventional bag-valve-mask ventilation.

Objective To test the hypothesis that prehospital advanced airway management is associated with favorable outcome after adult OHCA.

Design, Setting, and Participants Prospective, nationwide, population-based study (All-Japan Utstein Registry) involving 649 654 consecutive adult patients in Japan who had an OHCA and in whom resuscitation was attempted by emergency responders with subsequent transport to medical institutions from January 2005 through December 2010.

Main Outcome Measures Favorable neurological outcome 1 month after an OHCA, defined as cerebral performance category 1 or 2.

Results Of the eligible 649 359 patients with OHCA, 367 837 (57%) underwent bag-valve-mask ventilation and 281 522 (43%) advanced airway management, including 41 972 (6%) with endotracheal intubation and 239 550 (37%) with use of supraglottic airways. In the full cohort, the advanced airway group incurred a lower rate of favorable neurological outcome compared with the bag-valve-mask group (1.1% vs 2.9%; odds ratio [OR], 0.38; 95% CI, 0.36-0.39). In multivariable logistic regression, advanced airway management had an OR for favorable neurological outcome of 0.38 (95% CI, 0.37-0.40) after adjusting for age, sex, etiology of arrest, first documented rhythm, witnessed status, type of bystander cardiopulmonary resuscitation, use of public access automated external defibrillator, epinephrine administration, and time intervals. Similarly, the odds of neurologically favorable survival were significantly lower both for endotracheal intubation (adjusted OR, 0.41; 95% CI, 0.37-0.45) and for supraglottic airways (adjusted OR, 0.38; 95% CI, 0.36-0.40). In a propensity score–matched cohort (357 228 patients), the adjusted odds of neurologically favorable survival were significantly lower both for endotracheal intubation (adjusted OR, 0.45; 95% CI, 0.37-0.55) and for use of supraglottic airways (adjusted OR, 0.36; 95% CI, 0.33-0.39). Both endotracheal intubation and use of supraglottic airways were similarly associated with decreased odds of neurologically favorable survival.

Conclusion and Relevance Among adult patients with OHCA, any type of advanced airway management was independently associated with decreased odds of neurologically favorable survival compared with conventional bag-valve-mask ventilation.

Point of care analysis of intraosseous samples

Some good news for remote, rural, prehospital, and retrieval medicine clinicians who rely on point of care testing with the i-STAT® device. An animal study confirmed the reliability of testing aspirates from intraosseous samples taken from the tibia(1).

This is also good news for hospital practitioners when it comes to the acquisition of blood gas results, since there are concerns over the potential damage to blood gas analysers by bone marrow contents in the samples.

The researchers tested blood gases, acid–base status, lactate, haemoglobin, and electrolytes, and compared these with results from an arterial sample.

There was no malfunction of the equipment. Most of the acid–base parameters showed discrepancies between arterial and osseous samples: the average pH and base excess were consistently lower whilst pCO2 and lactate were higher in the intraosseous samples compared to the arterial. However the overall small degree and predictable direction of discrepancy in these values should preserve the clinical usefulness of intraosseous gases if these findings can be replicated in human subjects. pO2 was obviously very different between osseous and arterial samples.

They noted that aspiration of intraosseous samples was generally straightforward, especially immediately after placement of the cannulae, but on a few occasions more forceful aspiration was needed. They point out that this could possibly cause cellular lysis and affect the potassium analysis.

The authors consider the issue of how much aspirate should be discarded before taking a sample after intraosseous cannula insertion, and refer to a prior study which suggested that 2mL is adequate.

  • Intraosseous aspirate can be tested on an i-STAT® point-of-care analyser
  • Haemoglobin and electrolytes show good correlation with arterial samples
  • Acid-base, pCO2, and lactate differ slightly from arterial results but in a predictable direction and results are still likely to be clinically useful in an emergency
  • It may be worth discarding the first 2 ml of aspirate
  • These results require validation in human subjects

Analysis of intraosseous samples using point of care technology–an experimental study in the anaesthetised pig
Resuscitation. 2012 Nov;83(11):1381-5

BACKGROUND: Intraosseous access is an essential method in emergency medicine when other forms of vascular access are unavailable and there is an urgent need for fluid or drug therapy. A number of publications have discussed the suitability of using intraosseous access for laboratory testing. We aimed to further evaluate this issue and to study the accuracy and precision of intraosseous measurements.

METHODS: Five healthy, anaesthetised pigs were instrumented with bilateral tibial intraosseous cannulae and an arterial catheter. Samples were collected hourly for 6h and analysed for blood gases, acid base status, haemoglobin and electrolytes using an I-Stat point of care analyser.

RESULTS: There was no clinically relevant difference between results from left and right intraosseous sites. The variability of the intraosseous sample values, measured as the coefficient of variance (CV), was maximally 11%, and smaller than for the arterial sample values for all variables except SO2. For most variables, there seems to be some degree of systematic difference between intraosseous and arterial results. However, the direction of this difference seems to be predictable.

CONCLUSION: Based on our findings in this animal model, cartridge based point of care instruments appear suitable for the analysis of intraosseous samples. The agreement between intraosseous and arterial analysis seems to be good enough for the method to be clinically useful. The precision, quantified in terms of CV, is at least as good for intraosseous as for arterial analysis. There is no clinically important difference between samples from left and right tibia, indicating a good reproducibility.

Lifting the Fogg on ED Intubaton

Fellow retrieval specialist and Royal North Shore Hospital emergency physician Dr Toby Fogg and coauthors have published their audit of intubations in an Australian Emergency Department(1). More important than the results themselves is that the process of monitoring ones practice inevitably leads to improvements. For example, at Toby’s institution an intubation checklist has been introduced since the audit began. Other Australasian EDs are encouraged to participate using the free resources at airwayregistry.org.au.

Recently we have also seen the publication of Korean registry data on paediatric intubations performed in 13 academic EDs over 5 years(2), in which first pass success rates (overall 67.6%) were higher with emergency physicians compared with paediatricians. Interestingly, a rapid sequence intubation technique was only used in 22.4% of intubations, which was more likely to be used by emergency physicians and was associated with a greater likelihood of first pass success.

This relatively low first pass success rate is reminiscent of the American study published in September(3) which raised some eyebrows with its 52% first pass intubation success rates in a paediatric ED, and which also showed that attending-level providers were 10 times more likely to be successful on the first attempt than all trainees combined. Possible reasons for such a low first pass success rate compared with adult registry data include the rigorous video analysis method used, or perhaps more likely that paediatric emergency subspecialists are exposed to fewer critical procedures, resuscitations, and intubations than their general emergency medicine counterparts(4).

As a specialty we must continue to seek to do better, and I salute all these brave authors who are telling it like it is. Particularly with children, whose airways are relatively easy, we have to develop the training, preparation, supervision, monitoring and feedback to aim for as high a success rate as possible.

Study authors Toby Fogg and Nick Annesley demonstrate the 'Happiness Triad'

1. Prospective observational study of the practice of endotracheal intubation in the emergency department of a tertiary hospital in Sydney, Australia
Emerg Med Australas. 2012 Dec;24(6):617-24

OBJECTIVE: To describe the practice of endotracheal intubation in the ED of a tertiary hospital in Australia, with particular emphasis on the indication, staff seniority, technique, number of attempts required and the rate of complications.

METHODS: A prospective observational study.

RESULTS: Two hundred and ninety-five intubations occurred in 18 months. Trauma was the indication for intubation in 30.5% (95% CI 25.3-36.0) and medical conditions in 69.5% (95% CI 64.0-74.5). Emergency physicians were team leaders in 69.5% (95% CI 64.0-74.5), whereas ED registrars or senior Resident Medical Officers made the first attempt at intubation in 88.1% (95% CI 83.9-91.3). Difficult laryngoscopy occurred in 24.0% (95% CI 19.5-29.3) of first attempts, whereas first pass success occurred in 83.4% (95% CI 78.7-87.2). A difficult intubation occurred in 3.4% (95% CI 1.9-6.1) and all patients were intubated orally in five or less attempts. A bougie was used in 30.9% (95% CI 25.8-36.5) of first attempts, whereas a stylet in 37.5% (95% CI 32.1-43.3). Complications occurred in 29.0% (95% CI 23.5-34.1) of the patients, with desaturation the commonest in 15.7% (95% CI 11.9-20.5). Cardiac arrest occurred in 2.2% (95% CI 0.9-4.4) after intubation. No surgical airways were undertaken.

CONCLUSION: Although the majority of results are comparable with overseas data, the rates of difficult laryngoscopy and desaturation are higher than previously reported. We feel that this data has highlighted the need for practice improvement within our department and we would encourage all those who undertake emergent airway management to audit their own practice of this high-risk procedure.

2. The factors associated with successful paediatric endotracheal intubation on the first attempt in emergency departments: a 13-emergency-department registry study
Resuscitation. 2012 Nov;83(11):1363-8

BACKGROUND: We investigated which factors are associated with successful paediatric endotracheal intubation (ETI) on the first attempt in emergency department (EDs) from multicentre emergency airway registry data.

METHODS: We created a multicentre registry of intubations at 13 EDs and performed surveillance over 5 years. Each intubator filled out a data form after an intubation. We defined “paediatric patients” as patients younger than 10 years of age. We assessed the specialty and level of training of intubator, the method, the equipment, and the associated adverse events. We analysed the intubation success rates on the first attempt (first-pass success, FPS) based on these variables.

RESULTS: A total of 430 ETIs were performed on 281 children seen in the ED. The overall FPS rate was 67.6%, but emergency medicine (EM) physicians showed a significantly greater success rate of 74.4%. In the logistic regression analysis, the intubator’s specialty was the only independent predictive factor for paediatric FPS. In the subgroup analysis, the EM physicians used the rapid sequence intubation/intubation (RSI) method and Macintosh laryngoscope more frequently than physicians of other specialties. ETI-related adverse events occurred in 21 (7.2%) out of the 281 cases. The most common adverse event in the FPS group was mainstem bronchus intubation, and vomiting was the most common event in the non-FPS group. The incidence of adverse events was lower in the FPS group than in the non-FPS group, but this difference was not statistically significant.

CONCLUSIONS: The intubator’s specialty was the major factor associated with FPS in emergency department paediatric ETI, The overall ETI FPS rate among paediatric patients was 67.6%, but the EM physicians had a FPS rate of 74.4%. A well structured airway skill training program, and more actively using the RSI method are important and this could explain this differences.

3.Rapid sequence intubation for pediatric emergency patients: higher frequency of failed attempts and adverse effects found by video review.
Ann Emerg Med. 2012 Sep;60(3):251-9

STUDY OBJECTIVE: Using video review, we seek to determine the frequencies of first-attempt success and adverse effects during rapid sequence intubation (RSI) in a large, tertiary care, pediatric emergency department (ED).

METHODS: We conducted a retrospective study of children undergoing RSI in the ED of a pediatric institution. Data were collected from preexisting video and written records of care provided. The primary outcome was successful tracheal intubation on the first attempt at laryngoscopy. The secondary outcome was the occurrence of any adverse effect during RSI, including episodes of physiologic deterioration. We collected time data from the RSI process by using video review. We explored the association between physician type and first-attempt success.

RESULTS: We obtained complete records for 114 of 123 (93%) children who underwent RSI in the ED during 12 months. Median age was 2.4 years, and 89 (78%) were medical resuscitations. Of the 114 subjects, 59 (52%) were tracheally intubated on the first attempt. Seventy subjects (61%) had 1 or more adverse effects during RSI; 38 (33%) experienced oxyhemoglobin desaturation and 2 required cardiopulmonary resuscitation after physiologic deterioration. Fewer adverse effects were documented in the written records than were observed on video review. The median time from induction through final endotracheal tube placement was 3 minutes. After adjusting for patient characteristics and illness severity, attending-level providers were 10 times more likely to be successful on the first attempt than all trainees combined.

CONCLUSION: Video review of RSI revealed that first-attempt failure and adverse effects were much more common than previously reported for children in an ED.

4. A is for airway: a pediatric emergency department challenge.
Ann Emerg Med. 2012 Sep;60(3):261-3