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Critical Care Journal Club

(Click on title to be directed to posting, most recent listed first)

November 2017 Phoenix Critical Care Journal Club
Tucson Critical Care Journal Club: Albumin Use in the Critical Care Unit
May 2016 Phoenix Critical Care Journal Club: Oxygen Therapy
November 2015 Tucson Critical Care Journal Club: Atrial Fibrillation in
September 2015 Phoenix Critical Care Journal Club: Goal-Directed
Therapy and DNR
June 2015 Phoenix Critical Care Journal Club: Interventions in ARDS
February 2015 Phoenix Critical Care Journal Club: Intracranial Pressure
Monitoring for Fulminant Liver Failure
August 2014 Tucson Critical Care Journal Club: Bacteremia in Cardiac 
July 2014 Phoenix Critical Care Journal Club: Predicting the Future
April 2014 Tucson Critical Care Journal Club: Early Goal-Directed
April 2014 Phoenix Critical Care Journal Club: Early Goal-Directed
March Critical Care Journal Club: Sequelae of Critical Care
February 2014 Phoenix Critical Care Journal Club: Subgroup Analysis
January 2014 Critical Care Journal Club
November 2013 Critical Care Journal Club
September 2013 Banner Good Samaritan / Phoenix VA Critical Care
   Journal Club
September 2013 Tucson Critical Care Journal Club: Early
August 2013 Critical Care Journal Club: Less is More
July 2013 Critical Care Journal Club
April 2013 Critical Care Journal Club
March 2013 Critical Care Journal Club
February 2013 Critical Care Journal Club
January 2013 Critical Care Journal Club
December 2012 Critical Care Journal Club
November 2012 Critical Care Journal Club
October 2012 Critical Care Journal Club
September 2012 Critical Care Journal Club
August 2012 Critical Care Journal Club
July 2012 Critical Care Journal Club
June 2012 Critical Care Journal Club
May 2012 Critical Care Journal Club
April 2012 Critical Care Journal Club
February 2012 Critical Care Journal Club
January 2012 Critical Care Journal Club
December 2011 Critical Care Journal Club 
November 2011 Critical Care Journal Club
September 2011 Critical Care Journal Club 
August 2011 Critical Care Journal Club 
July 2011 Critical Care Journal Club
June 2011 Critical Care Journal Club 
April 2011 Critical Care Journal Club
March 2011 Critical Care Journal Club
February 2011 Critical Care Journal Club
November 2010 Critical Care Journal Club
October 2010 Critical Care Journal Club


Both the Phoenix Good Samaritan/VA and the University of Arizona fellows previously had a periodic critical care journal club in which current or classic articles were reviewed and discussed. A brief summary was written of each discussion describing the article and the strengths and weaknesses of each article.



November 2017 Phoenix Critical Care Journal Club

After a hiatus, the Banner University Medical Center Phoenix/Phoenix VA critical care club was held on November 22. We reviewed recent guidelines from the ATS/ERS on mechanical ventilation for the adult respiratory syndrome (ARDS); a recent article on lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP; and a review of dyssynchronous mechanical ventilation.

Mancebo J, Meade MO, McAuley DF, et al. An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2017 May 1;195(9):1253-63. [CrossRef] [PubMed]

The ATS/ERS committee made a strong recommendation for mechanical ventilation using lower tidal volumes (4–8 ml/kg predicted bodyweight) and lower inspiratory pressures (plateau pressure,30 cm H2O) (moderate confidence in effect estimates). However, on page 1257 the summary of the evidence seems dyssynchronous with the recommendations.  “Mechanical ventilation strategies that limit tidal volumes [LTV] and inspiratory pressures have been compared with traditional strategies in nine RCTs [randomized controlled trials] including 1,629 patients. …Mortality was not significantly different for patients receiving an LTV compared with traditional strategies (seven studies, 1,481 patients; risk ratio [RR], 0.87; 95% CI, 0.70–1.08; moderate confidence). There were also no significant differences in barotrauma (three studies, 1,029 patients; RR, 0.96; 95% CI, 0.67–1.37; low confidence) or ventilator-free days (VFDs) (two studies, 977 patients; 0.03 more VFDs; 95% CI, 25.88 to 5.95; low confidence) between groups.

The committee goes on to strongly recommend that patients with severe ARDS, have prone positioning for more than 12 h/d (moderate confidence in effect estimates). “Prone positioning has been evaluated in eight RCTs, including 2,129 patients but there was no significant difference in mortality for patients in the prone versus supine groups. …However, in prespecified subgroup analyses (based on proning duration, ARDS severity, concomitant LTV ventilation), prone positioning reduced mortality in trials with prone duration greater than 12 h/d (five studies, 1,002 patients; RR, 0.74; 95% CI, 0.56–0.99; high confidence) and patients with moderate or severe ARDS (five studies, 1,006 patients; RR, 0.74; 95% CI, 0.54–0.99.”

For patients with moderate or severe ARDS, the committee made a strong recommendation against routine use of high-frequency oscillatory ventilation (high confidence in effect estimates) and conditional for higher positive end-expiratory pressure (moderate confidence in effect estimates) and recruitment maneuvers (low confidence in effect estimates). In each there was no difference in mortality.

It is difficult to understand why the committee made strong or even moderate recommendations when the considerable available evidence suggests that most make no difference in mortality or secondary end points such as barotrauma or ventilator-free days.

Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators. Effect of lung recruitment and titrated positive end-expiratory pressure (peep) vs low peep on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA. 2017 Oct 10;318(14):1335-45. [CrossRef] [PubMed]

Many have advocated lung recruitment maneuvers and positive end-expiratory pressure (PEEP) titration to the best respiratory-system compliance in patients with moderate or severe ARDS. Although logical, the effects of these maneuvers on clinical outcomes remain uncertain. The authors conducted a multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries enrolling adults with moderate to severe ARDS. An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory-system compliance (n = 501; experimental group) was compared with control strategy of low PEEP (n = 509).

Compared with the control group, the experimental group strategy increased 28-day all-cause mortality, decreased the number of mean ventilator-free days, increased the risk of pneumothorax requiring drainage, and increased the risk of barotrauma. There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality. Based on this well-designed trial, we concluded that we would not use lung recruitment maneuvers and PEEP titration in ARDS patients.

Gilstrap D, MacIntyre N. Patient-ventilator interactions. Implications for clinical management. Am J Respir Crit Care Med. 2013 Nov 1;188(9):1058-68. [CrossRef] [PubMed]

This is a review article on dyssynchronous mechanical ventilation where ventilator support does not match patient demands. Dyssynchrony imposes high pressure loads on ventilator muscles, promoting muscle overload/fatigue and increasing sedation needs. The authors discuss maneuvers that can enhance synchrony including adjustments of the trigger variable, the use of pressure versus fixed flow targeted breaths, and manipulations of the cycle variable. The authors point out that many dyssynchronies are subtle and of little clinical relevance, but can produce patient discomfort and are a frequently cited indication for the administration of sedatives. Determining the prevalence of patient–ventilatory dyssynchrony is difficult as studies examining this question have involved varying patient populations, definitions of dyssynchrony, methods of detection, duration and timing of observation, and ventilatory modes.  However, a retrospective evaluation of the National Institutes of Health (NIH) ARDS Network small VT study reported cycling dyssynchronies associated with double triggering in 9.7% of all breaths analyzed suggesting it may be relatively common.

The authors discuss two new approaches to improving patient ventilatory interactions: proportional assist ventilation (PAV) and neurally adjusted ventilatory assist (NAVA). PAV breaths are patient-initiated breaths triggered in a conventional way using circuit pressure or flow sensors. Thereafter, the ventilator continues to monitor flow and volume demanded by the patient and puts a clinician-set “gain” on this demand to augment flow and pressure in proportion to the desired reduction in the patient’s work of breathing. NAVA requires a unique esophageal catheter with an array of diaphragm electromyogram (EMG) sensors. These sensors detect the onset, intensity, and termination of inspiratory efforts directly. Like PAV, a clinician-set gain is then applied that determines flow and pressure delivery in proportion to the EMG signal.

Although there was general agreement that it is unclear if correcting dyssynchrony improves outcomes, most thought this was an excellent, well-balanced review article.

Richard A. Robbins MD and Robert A. Raschke MD

University of Arizona College of Medicine Phoenix

Phoenix, AZ USA

Cite as: Robbins RA, Raschke RA. November 2017 Phoenix critical care journal club. Southwest J Pulm Crit Care. 2017;15(6):269-70. doi: PDF 


Tucson Critical Care Journal Club: Albumin Use in the Critical Care Unit

Lyu PF, Hockenberry JM, Gaydos LM, Howard DH, Buchman TG, Murphy DJ. Impact of a sequential intervention on albumin utilization in critical care. Crit Care Med. 2016 Jul;44(7):1307-13. [CrossRef] [PubMed]

Albumin use for volume resuscitation in critically ill patients has been a hotly contested topic for decades (1). Widespread use of this expensive medicine in some settings has been based on perceived benefits without strong supporting evidence (2 ). Providing patient centered, evidence based, high value care is an expectation of most healthcare entities thus leading many hospitals to consider the cost effectiveness of their practices (3). One area of interest involves the use of albumin for volume resuscitation. Provider education has not changed practice; therefore, novel approaches to align provider behavior with evidence-based standards are necessary (4-6).

In this pre-post quasi-experimental study with historical controls, investigators at Emory Critical Care Center (ECCC) hypnotized that a sequentially implemented multifaceted intervention would reduce albumin use without increasing mortality. The study was conducted between September 2011 and August 2014 in eight intensive care units (ICUs; two medical, two cardiothoracic, two neuroscience, one surgical, and one coronary unit). The study population included all ICU admissions (ICU readmissions and liver transplant patients excluded).

The first year was an observation period to generate pre-intervention data. In year one of the intervention period, a monthly albumin utilization feedback report was distributed to all units while the intensivists, nurse practitioners and physician assistants received financial incentives to reduce albumin use. Both the financial incentive and the feedback reports ended after the first intervention year.

In the second intervention year, evidence based guidelines for albumin use were incorporated in the computerized ordering system such that providers had to select an indication for albumin use.

A total of 22,004 admissions were included, 7,303 in the baseline year, and 14,701 the 2-year intervention period. Patient characteristics were similar between the two periods. After adjusting for differences in patient characteristics between the baseline and intervention periods, the intervention was associated with a 42% decrease in the number of albumin orders per ICU admission (p < 0.001). This adjusted effect included a relative 18% reduction in the probability of the patient receiving any albumin order (p < 0.001) and a relative 29% reduction in the number of orders per admission among patients receiving at least one order (p < 0.001).  The team estimated that reductions in albumin orders translated into mean savings of $171 per admission while aggregate direct cost savings were nearly $2.5M in the 2-year period. Adjusted analysis found no difference in ICU mortality (p = 0.96) or in-hospital mortality (p = 0.96).  The study concluded that the intervention reduced albumin use without compromising patient safety.

This study was done in five different ICU settings, which provided great generalizability, however, this can mask variable effects in different units. Even though the pre-intervention and post-intervention groups had comparable characteristics, the pre-post design provides weaker evidence than randomized controlled trials (RCTs) due to the lack of randomization, which can threaten the internal validity. During the 3-year intervention period, external factors such as new evidence or changes in guidelines in the medical literature, concurrent quality projects or new hospital policies could impact the trends of albumin use.

Given that the study did not collect data on the substitute fluids and related medications, money spent on incentives, providing a comprehensive cost-effectiveness analysis is not possible. It was interesting to see how the monetary incentives reduced average albumin use but did not change who received it, while the guidelines and integration in the ordering process appeared to impact both.

In summary, in this study, the investigators provided a unique perspective on how sequential multi faceted initiative can lead to practice change towards high value care and significant healthcare dollar savings without adversely affecting ICU or hospital mortality. It remains to be seen if this model can be replicated in other settings and if the newly developed habits are sustainable.

Huthayfa Ateeli MBBS, Christian Bime MD and Joe Gerald PhD

University of Arizona

Tucson, AZ


Patel A, Laffan MA, Waheed U, Brett SJ. Randomised trials of human albumin for adults with sepsis: systematic review and meta-analysis with trial sequential analysis of all-cause mortality. BMJ. 2014 Jul 22;349:g4561. [CrossRef] [PubMed]

  1. American Thoracic Society. Evidence-based colloid use in the critically ill: American Thoracic Society Consensus Statement. Am J Respir Crit Care Med. 2004;170(11):1247-1259. [CrossRef] [PubMed]
  2. Institute for Healthcare Improvement. IHI triple aim initiative. Available at: (accessed 11/11/16).
  3. Berenholtz S, Pronovost PJ. Barriers to translating evidence into practice. Curr Opin Crit Care. 2003 Aug;9(4):321-5. [CrossRef] [PubMed]
  4. Hewson-Conroy KM, Burrell AR, Elliott D, Webb SA, Seppelt IM, Taylor C, Glass P. Compliance with processes of care in intensive care units in Australia and New Zealand--a point prevalence study. Anaesth Intensive Care. 2011 Sep;39(5):926-35. [PubMed]
  5. Grol R, Grimshaw J. From best evidence to best practice: effective implementation of change in patients' care. Lancet. 2003 Oct 11;362(9391):1225-30. [CrossRef] [PubMed]

Cite as: Ateeli H, Bime C, Gerald J. Tucson critical care journal club: albumin use in the critical care unit. Southwest J Pulm Crit Care. 2016;13(5):238-9. doi: PDF 


May 2016 Phoenix Critical Care Journal Club: Oxygen Therapy

Panwar R, Hardie M, Bellomo R, Barrot L, Eastwood GM, Young PJ, Capellier G, Harrigan PW, Bailey M; CLOSE Study Investigators; ANZICS Clinical Trials Group. Conservative versus liberal oxygenation targets for mechanically ventilated patients. A pilot multicenter randomized controlled trial. Am J Respir Crit Care Med. 2016 Jan 1;193(1):43-51. [CrossRef] [PubMed]

We continue to debate the appropriate level of oxygenation for a variety of patients. This study attempted to address the question of appropriate oxygenation targets for intensive care unit (ICU) patients. At four multidisciplinary ICUs, 103 adult patients were randomly allocated to either a conservative oxygenation strategy with target oxygen saturation as measured by pulse oximetry (SpO2) of 88-92% (n = 52) or a liberal oxygenation strategy with target SpO2 of greater than or equal to 96% (n = 51). There were no significant between-group differences in any measures of new organ dysfunction, or ICU or 90-day mortality. Although the study is underpowered, it does support the concept that a conservative oxygen strategy might be appropriate.

Eastwood GM, Tanaka A, Espinoza ED, Peck L, Young H, Mårtensson J, Zhang L, Glassford NJ, Hsiao YF, Suzuki S, Bellomo R. Conservative oxygen therapy in mechanically ventilated patients following cardiac arrest: A retrospective nested cohort study. Resuscitation. 2016 Apr;101:108-14. [CrossRef] [PubMed]

In mechanically ventilated (MV) cardiac arrest (CA) survivors admitted to the intensive care unit (ICU) avoidance of hypoxia is considered crucial. However, avoidance of hyperoxia may also be important since some prior studies have suggested that high levels of oxygenation decrease survival. The same investigators as the study discussed above, evaluated the introduction of conservative oxygen therapy (target SpO2 88-92% using the lowest FiO2) during MV for resuscitated CA patients admitted to the ICU. 100 patients (50 in each group). ICU length of stay was significantly shorter for conservative group patients (p=0.04). There was no difference in the proportion of survivors discharged from hospital with good neurological outcome (14/23 vs 12/22 patients, p=0.67). As in the previous study, this study was also underpowered but does support the feasibility and physiological safety of conservative oxygen therapy in patients admitted to ICU for MV support after cardiac arrest.

Cabello JB, Burls A, Emparanza JI, Bayliss S, Quinn T. Oxygen therapy for acute myocardial infarction. Cochrane Database Syst Rev. 2013 Aug 21;(8):CD007160 [Crossref] [PubMed]

Oxygen is widely prescribed for patients with acute myocardial infarction (AMI) although it has been suggested it may do more harm than good. Previous systematic reviews have concluded that there was insufficient evidence to know whether oxygen reduced, increased or had no effect on heart ischemia or infarct size, as did our original Cochrane review on this topic in 2010. The authors used the Cochrane Library to search for randomized controlled trials of oxygen in patients with suspected or proven AMI. The updated search identified one new trial. In total, four trials involving 430 participants were included and 17 deaths occurred. The pooled RR of death was 2.05 (95% CI 0.75 to 5.58) in an intention-to-treat analysis and 2.11 (95% CI 0.78 to 5.68) in participants with confirmed AMI. While suggestive of harm, the small number of deaths recorded means that this could be a chance occurrence.


Many of us were surprised that there is ongoing argument over use of oxygen. Although it is cheap and easy to administer, the three articles cited suggest that a conservative approach is equally effective. None of the trials were sufficiently powered to draw a conclusion. The possibility exists that oxygen might do harm but this will require further and larger (and more expensive) trials.

It is worth pointing out that these studies do not necessarily apply to other patients. An acute exacerbation of chronic obstructive pulmonary disease with hypercarbia may be different. A recent study demonstrated that titrated oxygen treatment significantly reduced mortality, hypercapnia, and respiratory acidosis compared with high flow oxygen in acute exacerbations of chronic obstructive pulmonary disease (1). Since pulse oximeters are nearly universally available in the US to guide therapy, it seems reasonable to use titrated oxygen whenever possible.

Richard A. Robbins MD and Robert A. Raschke MD

Phoenix Pulmonary and Critical Care Research and Education Foundation

Banner University Medical Center-Phoenix

Phoenix, AZ


  1. Austin MA, Wills KE, Blizzard L, Walters EH, Wood-Baker R. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ. 2010 Oct 18;341:c5462. [CrossRef] [PubMed]

Cite as: Robbins RA, Raschke RA. May 2016 Phoenix critical care journal club. Southwest J Pulm Crit Care. 2016;12(6):231-2. doi: PDF


November 2015 Tucson Critical Care Journal Club: Atrial Fibrillation in Sepsis

Walkey AJ, Evans SR, Winter MR, Benjamin EJ. Practice patterns and outcomes of treatments for atrial fibrillation during sepsis: A propensity-matched cohort study. Chest. 2015 Aug 13. [CrossRef]

Sepsis is a major public health concern in the United States (1). Nearly one-third of in-hospital deaths are the result of sepsis (2). Atrial fibrillation (A-fib) is the most common arrhythmia in sepsis and its development portends worse outcomes (3). Current guidelines recommend cardioversion in hemodynamically unstable patients with sepsis; however, there is scant evidence to guide the choice between amiodarone, beta-blockers, calcium-channel blockers, and digoxin (4). In patients with decompensated heart failure, digoxin and amiodarone are preferred over beta-blockers and calcium channel blockers (4). In patients with multiple organ failure there is no evidence to suggest any one agent is superior to the others. This study by Walkey et al. sought to identify current practice patterns in the pharmacologic treatment of A-fib among hospitalized patients with sepsis and to compare outcomes after controlling for potential confounding variables.

This retrospective cohort study used a nationally representative source of hospital billing data from 2010-2013 to examine outcomes among patients admitted with sepsis who received antibiotics on the first day of hospitalization and had either pre-existing or new-onset A-fib. Use of intravenous beta-blockers, calcium channel blockers, cardiac glycosides, and amiodarone within 14 days of admission was also examined. Those who received oral medications or those who received multiple agents on the same day were excluded. Patient- and hospital-level characteristics were also obtained from billing data. The primary outcome was in-hospital mortality.    

Propensity scoring was used to adjust for measured confounding and an instrumental variable approach was used to account for unmeasured confounding. Outcomes among those treated with beta-blockers were then compared to those treated with other classes of medication.

Approximately 540,000 patients were hospitalized with sepsis and 113,511 had sepsis and A-fib. Approximately 40,000 received intravenous therapy and comprised the analytic sample. Of those patients included, 49% were women and 76% were white; the average age was 77 years. Calcium channel blockers were the most frequently used initial therapy (36%), followed by beta-blockers (28%), digoxin (20%), and amiodarone (16%).

In comparison to patients treated initially with beta-blockers, those receiving calcium channel blockers were more likely to be younger, female, and white; they also had fewer comorbid conditions. Patients initially treated with beta-blockers were less likely to experience in-hospital mortality as compared to those initially treated with calcium channel blockers, 18.3% versus 20.0%, respectively (RR 0.92, 0.86-0.97). There was no effect modification based on pre-existing or new-onset A-fib or the presence of heart failure; however, outcomes were better among patients treated with a vasopressor as compared to those not similarly treated (p=0.02).

Patients receiving digoxin were typically older and more likely to have heart failure, COPD, malignancy, or shock than those receiving beta-blockers. Beta-blocker use was associated with lower in-hospital mortality than digoxin use, 20.5% versus 25.7%, respectively (RR 0.79, 0.75-0.84). There was no effect modification by A-fib onset, vasopressor use, or heart failure.

Patients receiving amiodarone were more likely to be critically ill or have heart failure, new onset A-fib, malignancy, or acute organ failure. Beta-blocker use was associated with lower mortality as compared to amiodarone use, 27% versus 42%, respectively (RR 0.65, 0.61, 0.69). There was no effect modification based on onset of A-fib or presence of heart failure; however, outcomes were better among those with concomitant treatment with vasopressors (p=0.003).

Overall, greater hospital-level use of beta-blockers was associated with reduced individual mortality (RR 0.67, 0.58- 0.79). These data support the conclusion that beta-blocker use among patient with sepsis and A-fib was associated with statistically and clinically significant reductions in in-hospital mortality irrespective of vasopressor use, timing of A-fib, or presence of heart failure.

Nevertheless, the study relied on an observational design which is subject to bias and confounding. However, the analytic approach used two rigorous methodologies, propensity scoring and instrumental variable, to account for measured and unmeasured confounding, respectively. More rigorous data will only come from a large, multi-center, randomized controlled trial. Unfortunately, such a trial will be expensive and will take many years to yield results. How should today’s clinicians respond given at least some risk that these results may turn out to be spurious? In situations when beta-blockers are not clearly contraindicated, it seems reasonable to recommend using beta-blockers first realizing that doing so does not preclude subsequently using another agent to achieve the desired therapeutic goal. While observational data would not be sufficient to overturn evidence from randomized controlled trials, in this case, no such data exist. Given the consistency of the findings, it is reasonable to ask whether greater use of beta-blockers in the treatment of severe sepsis might be warranted even in the absence of A-fib.

Ryan R. Nahapetian MD, Joe Gerald PhD

Pulmonary, Allergy, Critical Care, & Sleep Medicine

University of Arizona

Tucson, AZ  


  1. Walkey AJ, Lagu T, Lindenauer PK. Trends in sepsis and infection sources in the United tates: a population based study. Ann Am Thorac Soc. 2015; 2015;12:216-20. [CrossRef] [PubMed]
  2. Liu V, Escobar GJ, Greene JD, Soule J, Whippy A, Angus DC, Iwashyna TJ. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA. 2014;312: 90-2. [CrossRef] [PubMed]
  3. Walkey AJ, Greiner MA, Heckbert SR, Jensen PN, Piccini JP, Sinner MF, Curtis LH, Benjamin EJ. Atrial fibrillation among Medicare beneficiaries hospitalized with sepsis: incidence and risk factors. Am Heart J. 2013;165:949-5.e3. [CrossRef] [PubMed]
  4. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1-76. [CrossRef] [PubMed] 

Cite as: Nahapetian RR, Gerald J. November 2015 Tucson critical care journal club: atrial fibrillation in sepsis. Southwest J Pulm Crit Care. 2015;11(6):266-8. doi: PDF


September 2015 Phoenix Critical Care Journal Club: Goal-Directed Therapy and DNR

Three articles were selected for this month's journal club. Two dealt with early goal-directed therapy for sepsis and came to essentially opposite conclusions. The third dealt with do not resuscitate (DNR) orders. Both topics are important to critical care physicians and have led to the development of guidelines.

Rhodes A, Phillips G, Beale R, et al. The Surviving Sepsis Campaign bundles and outcome: results from the International Multicentre Prevalence Study on Sepsis (the IMPreSS study). Intensive Care Med. 2015;41(9):1620-8. [CrossRef] [PubMed]

This was a prospective, observational, quality improvement study of compliance with the surviving sepsis campaign 3 and 6 hour bundles in patients with either severe sepsis or septic shock. The 3 hour bundle consists of measurement of lactate, obtaining blood cultures, administering broad spectrum antibiotics and administration or 30 mL/kg crystalloid for hypotension. The 6 hour bundle is composed of repeating the lactate, vasopressors for hypotension, measuring central venous pressure, and measuring central venous oxygen saturation. A total of 1794 patients from 62 countries were enrolled in the study with either severe sepsis or septic shock. Compliance with the bundle metrics was not high. Overall compliance with all the 3-h and 6-h bundle metrics was 19 % and 36% respectively.  Compliance with the 3-h and 6-h bundles was associated with lower hospital mortality than non-compliance (p < 0.001, both comparisons). Patients whose care included compliance with all of these metrics had a 40 % reduction in the odds of dying in hospital with the 3-h bundle and 36 % for the 6-h bundle.

The only therapeutic guidelines in the bundles are to administer antibiotics and to support the blood pressure first with fluids and then vasopressors if fluids do not correct the hypotension. Unless one rejects the germ theory, the only real therapeutic option is whether to administer fluids and/or vasopressors, or essentially early goal-directed therapy.

Angus DC, Barnato AE, Bell D, et al. A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators. Intensive Care Med. 2015;41(9):1549-60.  [CrossRef] [PubMed]

This was a meta analysis of the five randomized clinical studies of early goal-directed therapy for sepsis (n = 4735 patients). There was no effect on the primary mortality outcome (P = 0.9). The authors conclude that early goal-directed therapy is not superior to usual care for patients with septic shock but is associated with increased utilization of ICU resources.

In the context of the first study by Rhodes et al., one wonders how can this be? The first study found a statistically significant mortality benefit while the later study did not. This points out to a common problem evaluating medical literature-different study techniques measuring slightly different variables coming to different results. The first study was an observational study, while the later used randomized studies. The first study was by a group who promoted sepsis guidelines and has been accused of significant conflicts of interest over the use of activated protein C (1). Furthermore, the authors repeatedly overstated the evidence basis and benefits of the bundles. This weakens the authors' argument and makes one question whether there is confirmation bias or the tendency to interpret new evidence as confirmation of one's existing beliefs or theories. Of note is that the first author of the later article, Derek Angus, is a former member of the surviving sepsis campaign.

In our own groups we have differing opinions over early goal-directed therapy. However, regardless of our opinions, the evidence is conflicting and it is hard to fault usual care instead of goal-directed therapy in sepsis. In other words, early goal-directed therapy does not meet the evidence basis for a guideline at this time.

Fendler TJ, Spertus JA, Kennedy KF, et al. Alignment of do-not-resuscitate status with patients' likelihood of favorable neurological survival after in-hospital cardiac arrest. JAMA. 2015;314(12):1264-71. [CrossRef] [PubMed]

This was a prospective observational study to assess whether patients' or families' decisions for do-not-resuscitate (DNR) orders after a successful resuscitation from in-hospital cardiac arrest are aligned with the patient's expected prognosis. The authors identified 26,327 patients with return of spontaneous circulation after in-hospital cardiac arrest between. Each patient's likelihood of favorable neurological survival (i.e., without severe neurological disability) was calculated. DNR orders after in-hospital cardiac arrest were generally aligned with patients' likelihood of favorable neurological survival. Overall, 5944 (22.6%) patients had DNR orders within 12 hours. This group was older and had higher rates of comorbidities (all P < 0.05) than patients without DNR orders. The actual rate of favorable neurological survival was higher for patients without DNR orders than it was for those with DNR orders. This pattern of lower survival among patients with DNR orders was seen in every decile of expected prognosis. However, only one-third of patients with the worst prognosis had DNR orders.

The authors recommend that after patients survive an in-hospital cardiac arrest, discussions should occur about prognosis and preferences for future resuscitative efforts. We all agree but with the caveat that patients and their families do not necessarily follow, or should they be expected to follow, prediction equations for neurological survival. For many DNR is an emotional decision. Furthermore, if the prognosis is quite grim, the physician might not seek a DNR order reasoning the patient is unlikely to survive. There may also be personal or religious conflicts or a lack of confidence in the physician's recommendation for or against a DNR order.

Like the first article on early goal-directed therapy, the authors overstate their case using the phrase "get with the guidelines". The lack of total alliance with the expected neurological outcome is expected given the emotional and stressful situation and the uncertainty that occurs with a prediction equation or scale. Failure to recognize the many instances where there should be lack of agreement between DNR and expected outcome only reinforces those skeptical of hospitals and physicians motivation. Furthermore, it strengthens the perception that the medical community might be "pulling the plug on grandma" further eroding confidence in the physician.

Richard A. Robbins, MD


Southwest Journal of Pulmonary and Critical Care


  1. Eichacker PQ, Natanson C, Danner RL. Surviving sepsis--practice guidelines, marketing campaigns, and Eli Lilly. N Engl J Med. 2006;355(16):1640-2. [CrossRef] [PubMed] 

Cite as: Robbins RA. September 2015 Phoenix critical care journal club: goal-directed therapy and DNR. Southwest J Pulm Crit Care. 2015;11:153-5. doi: PDF