SJRHEM Journal Club Report Oct 2017

SJRHEM Journal Club Report Oct 2017

Allyson Cornelis, R1 iFMEM

Hosted by Dr Andrew Lohoar


Abstract:

Idarucizumab for Dabigatran Reversal — Full Cohort Analysis

Charles V. Pollack, Jr., M.D., Paul A. Reilly, Ph.D., Joanne van Ryn, Ph.D., John W. Eikelboom, M.B., B.S., Stephan Glund, Ph.D., Richard A. Bernstein, M.D., Ph.D., Robert Dubiel, Pharm.D., Menno V. Huisman, M.D., Ph.D., Elaine M. Hylek, M.D., Chak-Wah Kam, M.D., Pieter W. Kamphuisen, M.D., Ph.D., Jörg Kreuzer, M.D., Jerrold H. Levy, M.D., Gordon Royle, M.D., Frank W. Sellke, M.D., Joachim Stangier, Ph.D., Thorsten Steiner, M.D., Peter Verhamme, M.D., Bushi Wang, Ph.D., Laura Young, M.D., and Jeffrey I. Weitz, M.D.

N Engl J Med 2017; 377:431-441August 3, 2017DOI: 10.1056/NEJMoa1707278

 

BACKGROUND
Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran.

METHODS
We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time. Secondary end points included the restoration of hemostasis and safety measures.

RESULTS
A total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted thrombin time or the ecarin clotting time. In group A, 137 patients (45.5%) presented with gastrointestinal bleeding and 98 (32.6%) presented with intracranial hemorrhage; among the patients who could be assessed, the median time to the cessation of bleeding was 2.5 hours. In group B, the median time to the initiation of the intended procedure was 1.6 hours; periprocedural hemostasis was assessed as normal in 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%. At 90 days, thrombotic events had occurred in 6.3% of the patients in group A and in 7.4% in group B, and the mortality rate was 18.8% and 18.9%, respectively. There were no serious adverse safety signals.

CONCLUSIONS
In emergency situations, idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947.)

 

http://www.nejm.org/doi/full/10.1056/NEJMoa1707278

 


SJRHEM Journal Club Report

 

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Apneic Oxygenation – Report from SJRHEM Journal Club

This week Dr James French hosted a journal club on the following paper:

 

Am J Respir Crit Care Med. 2016 Feb 1;193(3):273-80. doi: 10.1164/rccm.201507-1294OC.

Randomized Trial of Apneic Oxygenation during Endotracheal Intubation of the Critically Ill.

Semler MW1, Janz DR2, Lentz RJ1, Matthews DT1, Norman BC1, Assad TR1, Keriwala RD1, Ferrell BA1, Noto MJ1, McKown AC1, Kocurek EG1, Warren MA1,Huerta LE1, Rice TW1; FELLOW Investigators and the Pragmatic Critical Care Research Group.

 

 

The Four Part Question was:

Patients: Adult patients in an American Medical ICU requiring Rapid Sequence Induction of Anesthesia

Intervention: Usual Care (that includes bagging, biped) with the addition of Hi Flo Nasal Cannula during the preoxygenation and intubation.

Comparison: Usual Care (that includes bagging, BiPap).

Outcome: Lowest Oxygen Saturation.

 

A Randomized open table intention to treat pragmatic trial in 146 patients.

The session was great fun and was greatly enriched by the telepresence of Dr George Kovacs of AIME fame. Many thanks to Dr Mark Tutc

Please find below a summary of the appraisal and subsequent discussions. The appraisal structure is from cebm.net

 

 

 

Bottom Line. High flow Nasal cannula is still likely to be of benefit in preventing desaturation during Rapid Sequence Induction of Anesthesia. 

Further Commentary By Dr George Kovacs – Here is an excerpt from our Oxygen delivery chapter:

There has been some controversy regarding the value of HFNO for apneic oxygenation with data from critical care patients demonstrating mixed results in the use of HFNO during the apneic period of an RSI. (Miguel-Montanes et al, 2014)(Vourc’h et al, 2015)(Patel & Nouraei, 2015)(Semler et al, 2016)(De Jong & Jaber, 2016) The findings that HFNO provided no added benefit in two of these studies seemed inconsistent with physiologic principles of preoxygenation and apneic oxygenation. Methodologically, there were inconsistencies in airway maintenance maneuvers between groups with the control group receiving PPV with an open airway as opposed to HFNO who had no airway opening documented. Vourc’h et al, 2015) Patients were reasonably well preoxygenated and commonly had PPV (NIV or BVM support) until laryngoscopy with relatively rapid intubation times (particularly in HFNO group) which would make the benefit of HFNO less apparent. (Semler et al, 2016) Collectively these studies do help us appreciate pearls and pitfalls of preoxygenation and apneic oxygenation using HFNO:

 

  1. For normal patients with normal lungs, preoxygenation is relatively easily achieved but is likely best performed with passive closed system BVM at 15 l/min for at least four minutes. For patients with increased minute ventilation needs, the addition of standard HFNO under a BVM with PEEP allows additional flow for preoxygenation and provides CPAP conditions.
  2. The use of dedicated HFNO (flows up to 60 l/) alone for preoxygenation may be an option for some patients. Standard HFNO (flows up to 15 l/min) should not be used alone for preoxygenation.
  3. During the induction period until full neuromuscular blockade is achieved and laryngoscopy begins, preoxygenation techniques, including HFNO delivery, require an actively opened airway (jaw thrust +/-OPA).  If not providing assisted ventilation during this phase, a closed system using BVM/PEEP with HFNO will likely provide the best ongoing preoxygenation conditions as the patient transitions to apnea.
  4. The addition of standard HFNO when performing assisted ventilations under a BVM/PEEP manual resuscitator or a mask delivering NIV is of questionable additional value. Benefit may come from distending (stenting) the upper airway, improving the nasopharyngeal oxygen reservoir and providing additional PEEP.
  5. Clinicians should be aware of the potential for leak from the use of HFNO under a mask. However, with a properly applied, tightly-fitted mask, leakage is likely negligible and insignificant.
  6. True apneic oxygenation provided by HFNO occurring during laryngoscopy will extend the apnea time. If preoxygenation was near complete and laryngoscopy is completed as it should be in under one minute, the value of ongoing HFNO may not be realized.
  7. The value and safety of HFNO is most recognized when difficulty is anticipated or encountered and allows more timethan would otherwise be available. This provides the clinician a less hurried, less stressed approach to the airway.
  8. HFNO should never be an excuse to “stay and play.” Time-based endpoints of  30-90 seconds, depending on preoxygenation status of the patient, should be predetermined as an end point and trigger active reoxygenation and “stop and think” time.
  9. HFNO is not a substitute for active reoxygenation between laryngoscopy attempts.

Further Commentary by Dr James French

Thats great, looking forward to getting the book!

With regards point 1 above 1.     “For normal patients with normal lungs, preoxygenation is relatively easily achieved but is likely best performed with passive closed system BVM at 15 l/min for at least four minutes. For patients with increased minute ventilation needs, the addition of standard HFNO under a BVM with PEEP allows additional flow for preoxygenation and provides CPAP conditions.”

I understand the excerpt is a physiological discussion so this may be covered in later chapters….

Even in the patient with no appreciated increased risks for hypoxia or assessed as having normal lungs, it may be logical to preoxygenate with a BVM, hi-flo nasal cannulas and a peep valve as routine for a number of system and human factors reasons, namely:

  1. The team have a checked and working “maximally aggressive” setup, the components of which are less vulnerable to errors of omission in the less adrenal pre-induction phase.
  2. The clinical sensitivity for identifying the “low risk for hypoxia patient” is likely to be poor. We know clinicians are have limited accuracy when assessing minute volume. The test characteristics of the pulmonary clinical exam are also variable. We also don’t have an accurate past medical history on many of our seriously ill patients. Or what happens in the adrenal state and as a fallible human we get the assessment wrong? We may therefore easily fail to identify the patient with sick lungs.
  3. If there is unexpected need to ventilate a patient with sudden onset shunt or deadspace secondary to an in procedure emergency e.g. laryngospasm, bronchospasm, aspiration, anaphylaxis, AMI, mucous plugging, unknown pulmonary tumour causing collapse and so on. In this situation being able to provide immediate peep, maximal FiO2, Ipap and rate could be lifesaving.
  4. The moments using the BVM as a tight mask in the pre-induction phase serve as a tactile substrate for visualization and near future planning of BVM practice.

Should all BVMs have a peep valve to ensure it is a closed circuit?!

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