December 2011 Critical Care Journal Club

Reference as: Raschke RA. December 2011 critical care journal club. Southwest J Pulm Crit Care 2011;3:173-6. (Click here for a PDF version of the journal club)

After a long intermission, critical care journal club is back! There really are some impactful articles to discuss this month, and the fellows did a great job reviewing them.  As always, we appreciate the faculty who participated in the discussion: Drs. Gerkin, Robbins, Bajo, and Khazin.

Amir Qassem et al.  Venous thromboembolism prophylaxis in hospitalized patients: A clinical practice guideline from the American College of Physicians. Ann Intern Med 2011;155:625-632. Reviewed in conference by Josh Jewel and Henry Leudy.  (Click here for PDF version of manuscript)

This article was recommended to us by Dr. Jay Blum.  The three recommendations of the ACP are based on extensive literature review. 

Recommendation 1: “ACP recommends assessment of the risk for thromboembolism and bleeding in medical (including stroke) patients prior to initiation of prophylaxis of venous thromboembolism (Grade: strong recommendation, moderate-quality evidence)”.

A meta-analysis of the evidence-base for venous thromboembolism (VTE) prophylaxis with heparin and LMWH was presented.  The statistical presentation was concise but understandable.  The meta-analysis of studies that looked at heparin prophylaxis in medical (non-stroke) patients is representative.  No statistical mortality benefit was demonstrated, but there was a significant reduction in pulmonary embolism (PE) balanced by a significant  increase in bleeding events - for every 1000 patients, heparin prophylaxis is estimated to prevent four PEs, but cause nine bleeds.  This risk/benefit ratio is likely to be strongly influenced in any individual patient by their specific health characteristics.  However, the authors state, “because no standard accepted formula for risk assessment exists to identify which medical patients are likely to benefit from VTE prophylaxis, the decision is best left to physician judgment”.

This conclusion is extended in a "Policy implication": “ACP does not support the application of performance measures in medical (including stroke) patients that promotes universal VTE prophylaxis regardless of risk”.

Recommendation 2: “ACP recommends pharmacologic prophylaxis with heparin or a related drug for VTE in medical (including stroke) patients unless the assessed risk of bleeding outweighs the likely benefits (Grade: Strong recommendation, moderate-quality evidence).”  

The risk reduction for PE will likely outweigh the increased risk of bleeding in most patients.  The first recommendation should not be interpreted as an argument for prophylactic nihilism. 

Recommendation 3: “ACP recommends against the use mechanical prophylaxis with graduated compression stockings for prevention of venous thromboembolism (Grade: strong recommendation, moderate quality evidence).”

There is little evidence from randomized controlled trials regarding clinical benefit of mechanical prophylaxis, and none of the available trials showed any benefit in mortality, PE or deep venous thrombosis.   This section seemed a little confused in distinguishing graduated compression stockings from intermittent pneumatic compression devices, but this seemed due to an inherent limitation of the available data.  Although not specifically mentioned in the recommendation, the discussion implies that there is no clear data regarding possible clinical benefit of intermittent pneumatic compression in medical patients.  In our hospital, many patients that have relative contraindications for heparin or LMWH are treated with intermittent pneumatic compression devices.  Many patients find them uncomfortable to wear, and taking them on and off may distract the nurses from more productive patient safety efforts.

VTE prevention is a major patient safety issue.  But the benefit/risk ratio for prophylaxis is not as robust as some expected.  Even strict compliance with targeted prophylaxis is not likely to impact hospital mortality, and universal prophylaxis would likely harm some patients. The overall rate of VTE prophylaxis should not be used as a physician performance measure, because prophylaxis should not be given to all patients.  Further studies are needed to better define patient groups in which the benefit clearly outweighs the risk.  In the meantime, most patients should still receive heparin prophylaxis, but physicians should use common sense in withholding prophylaxis from patients at increased risk of bleeding.

Brodie D, and Bacchetta M.  Extracorporeal membrane oxygenation in ARDS in adults. New Engl J Med 2011;365:1905-14.  Reviewed in conference by Emad Wissa. (Click here for abstract of mansucript)

It describes the many limitations of the literature, but offers a practical approach, focusing on several aspects of care that might improve our future ECMO performance.       

Evidence-based management of ARDS currently includes three strategies shown in randomized controlled trials to reduce mortality: low-tidal volume ventilation, conservative fluid therapy, and early use of neuromuscular blocking agents (we will review this article next month).  All other methods used to manage refractory hypoxemia, including high-frequency oscillation ventilation, inhaled nitric oxide, prone positioning, steroids, and ECMO are of uncertain clinical benefit.  There is no data that would allow these to be ranked in an algorithm, and therefore the decision to implement them, and what order to use them in, should depend on the clinician’s preference for the individual patient and the availability of resources.

Older clinical trials of ECMO are no longer pertinent due to dramatic technological advances. The recent CESAR trial showed a significant clinical benefit of transferring patients with severe ARDS to a center capable of providing ECMO, but did not directly compare ECMO to standard ventilator management. Guidelines from extracorporeal life support organization (ELSO) state that ECMO is recommended for patients suffering respiratory failure when the PaO2/FiO2 ratio is < 80, and should be considered when PaO2/FiO2 is < 150.  This is a reasonable approach at centers that offer ECMO, but does not represent a standard of care. 

Several technological advances may reduce adverse events associated with ECMO and thereby increase its benefit/risk ratio.  The advent of bicaval dual lumen catheters allows veno-venous ECMO to be implemented via a single vascular access.  More biocompatible materials and improved pump design have reduced the risks of thrombosis, disseminated intravascular coagulation and hemolysis - this translates into more conservative transfusion thresholds and reduced anticoagulation targets, which will likely reduce the risks of transfusion-related lung injury and bleeding.  

Perhaps the most important mechanism by which veno-venous ECMO might benefit a patient with ARDS is that it allows the lung to recover from ventilator-associated lung injury.  The authors recommend using very gentle  lung-protective ventilator settings during ECMO  i.e., pressure support with peak pressure of 20 cm H₂O, a rate of 10, and FiO₂ of 30%  - these settings typically produce tidal volumes below 4 mL/Kg ideal body weight, and theoretically should allow the lung a chance to heal.

Like any other life support modality, the mortality benefit of ECMO will become clear only when ECMO becomes safer than the alternatives.  In the near future, this advantage is likely only to occur in ARDS patients at highest risk for ventilator-associated lung injury, and only at centers which practice ECMO in the safest possible manner.

Hoeper MM, and Granton J.  Intensive care unit management of patients with severe pulmonary hypertension and right heart failure.  Am J Respir Crit Care Med  2011;184:1114-24.  Reviewed in conference by Roxanne Garciaorr. (Click here for abstract of manuscript)

The authors focused on patients with chronic pulmonary hypertension who suffer acute right heart failure.  For practical purposes, this group is largely comprised of patients with type 1 (pulmonary arterial hypertension) and type 4 (chronic thromboembolic pulmonary hypertension).

Right heart failure in patients with chronic pulmonary hypertension is often triggered by events such as medication noncompliance, tachyarrhythmias, infections, anemia, and pregnancy.  As the right ventricular ejection fails due to critical afterload and preload conditions, a vicious cycle begins in which systemic hypotension reduces right ventricular coronary perfusion, and a dilating right ventricle (RV) increasingly impinges on left ventricular (LV) filling.    

In some patients in this situation, the administration of IV fluids can benefit cardiac output by increasing RV preload.  But fluid management is complicated by the interdependence of the ventricles.  A fluid bolus that further dilates the RV might actually further impinge on LV filling, paradoxically reducing cardiac output.  The authors therefore recommend consideration of monitoring such patients with a Swan Ganz catheter.  It should be noted that the pulmonary artery wedge pressure (PAWP) may overestimate LV preload in the presence of a severely dilated RV.  In this case, the PAWP minus the right atrial pressure more closely approximates filling pressure of the LV.

Atrial fibrillation is poorly tolerated by patients with severe chronic pulmonary hypertension.  Rate control often doesn't adequately restore preload to the dilated RV that has become dependent on coordinated atrial contraction.  Medications typically used to achieve rate control, such as beta-blockers and Ca-channel blockers may worsen hypotension and further impair RV coronary perfusion.  Amiodarone may be tried, but the best course is often to proceed to electrical cardioversion.

Support may include measures such as dobutamine to improve systolic function, vasopressin or levophed to improve perfusion pressure, and transfusion to a hemoglobin of 10 g/dL.  RV afterload may be reduced by intravenous prostacyclin derivatives such as epoprostenol or by inhaled vasodilators such as nitric oxide or iloprost.  Endotracheal intubation should be avoided if at all possible - sedation drugs and alterations in intrathoracic pressure associated with positive pressure ventilation may precipitate cardiopulmonary arrest. 

The outcome of patients with acute right heart failure secondary to chronic pulmonary hypertension is critically dependent on a coordinated approach that is specific to a unique pathophysiology.  This paper should be studied in detail by all the fellows - the article is full of important clinical pearls, of which only a few are reviewed herein.

Robert A. Raschke, M.D.

Associate Editor, Critical Care Journal Club