Prognosis of septic shock

1192 Correspondence / American Journal of Emergency Medicine 35 (2017) 11901206

Prognosis of septic shock

We read with great interest the article by April et al. in the American Jour- nal of Emergency Medicine [1]. The authors compared in-hospital mortality among emergency department patients meeting trial-based criteria for septic shock based upon whether presenting with refractory hypotension versus hyperlactatemia. They found that mortality was 10.9% among patients with isolated refractory hypotension, 24.4% among patients with isolated hyperlactatemia, and 28.3% among patients with both. The results of this study are similar with recently published secondary analysis of the ARISE (Australian Resuscitation in Sepsis Evaluation) trial [2]. The ARISE study re- vealed that the participants enrolled on the basis of isolated hyperlactatemia had a higher 90-day mortality; were less likely to be discharged alive from both intensive care unit and hospital; had longer intensive care unit and hos- pital duration of stay; and received mechanical ventilation more often than participants with isolated refractory hypotension. These observations imply that a blood lactate >=4 mmol/L is likely an important independent marker of disease severity in sepsis; that it can be used for risk stratification and that it may be a candidate for the definition of septic shock. However, a singu- lar ideal biomarker has not yet been identified; an alternative approach is to shift research focus to determine the diagnostic relevancy of multiple bio- markers when used in concert. We think that sepsis often presents alongside other conditions and due to this complexity, a single ‘golden’ biomarker may not exist, thus research should shift more focus on to assessing the combined diagnostic and prognostic capabilities of multiple biomarkers such as lactate, procalcitonin, C-reactive protein, Natriuretic peptides, troponins and etc.

Funda Sungur Biteker, MD

Yatagan State Hospital, Department of Infectious Diseases and Clinical

Microbiology, Turkey

Oguzhan Celik, MD* Bulent Ozlek, MD Eda Ozlek, MD

Murat Biteker, MD, Associate Prof

Mugla University, Faculty of Medicine, Department of Cardiology, Turkey

*Corresponding author at: Mugla Sitki Kocman Universitesi Tip Fakultesi Orhaniye Mah. Haluk Ozsoy Cad., 48000 Mugla, Turkey E-mail address: [email protected] (O. Celik)

12 May 2017


April MD, Donaldson C, Tannenbaum LI, Moore T, Aguirre J, Pingree A, et al. Emergen- cy department septic shock patient mortality with refractory hypotension vs hyperlactatemia: a retrospective cohort study. Am J Emerg Med 2017 Apr 27. (pii: S0735-6757(17)30319-4).
  • Gotmaker R, Peake SL, Forbes A, Bellomo R, ARISE Investigators. Mortality is greater in septic patients with hyperlactatemia than with refractory hypotension. Shock 2017 Feb 28.
  • lactic acid production including neutrophil activation, sympathetic stimulation and high production of pyruvate in addition to many other normal physiologic processes [2]. Consequently, by itself lactate is an imperfect marker for guiding the treatment and prognostication of patients in septic shock.

    As the authors note, there are many additional biomarkers with potential value for screening, guiding therapy, and prognosticating outcomes among these critically ill patients. In addition to those biomarkers mentioned in the authors’ letter, the literature has also discussed the use of endothelial activators, acute phase reactants, and proadrenomedullin. Such biomarkers all have their own limitations with regards to accurate portrayal of patient physiology and assay availability. The literature discussing their use routinely emphasizes these drawbacks [3].

    Consideration of multiple biomarker levels together is certainly likely to be of greater clinical utility than their consideration in isolation. Future investigations of the use of multiple biomarkers in concert will ideally also incorporate basic measures of patient physiology and physical examination much like the various sepsis scoring systems such as the sys- temic inflammatory response syndrome (SIRS) criteria and the quick se- quential organ failure assessment (qSOFA). Yet, we must highlight that years of efforts to design such systems have nevertheless resulted in scores with significant limitations. There is a balance to be struck between complexity in incorporating more clinical information to yield greater Prognostic accuracy versus simplicity for each of use by clinicians. In fact, it appears that simplified scores such as qSOFA are least accurate in prognosticating outcomes in sepsis among those patients in septic shock whose physiologic derangements are most severe [4].

    We welcome the authors’ call for further research on alternative combinations of laboratory biomarkers and other clinical data to better prognosticate patients with septic shock. Yet at the same time we are skeptical that any finite collection of laboratory tests, physiolog- ical measurements, and examination findings will be found in the near future which truly revolutionizes sepsis care. Indeed, sepsis is a complex process with clinical outcomes highly dependent upon a patient’s premorbid functional condition, virulence of the infectious organisms, and genetic factors. These factors precede even initial patient evalua- tion, let alone laboratory tests and Clinical score calculations, making it incredibly challenging to develop infallible decision aids for diagnosis, management, and prognostication. We believe the use of such data must always be accompanied by careful bedside evaluation and moni- toring with sound clinical judgment to optimize patient survival.


    The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the

    U.S. Army Medical Department, the U.S. Army Office of the Surgeon

    General, the Department of the Army and Department of Defense or the U.S. Government.



    The authors reply: Prognosis of septic shock

    Conflicts of interest


    Michael D. April, MD, DPhil, MSc

    We thank the authors for their interest in our paper, “Emergency Depart- ment Septic Shock Patient Mortality with Refractory Hypotension vs Hyperlactatemia: A Retrospective Cohort Study” [1]. We certainly agree with their observation that while our results suggest that lactate can serve as an important physiologic and prognostic marker, considered in isolation it may fail to adequately capture any given patient’s clinical status. Providers may generally presume that an elevated lactate level encountered in an emer- gency department (ED) patient portends an increased risk of mortality sec- ondary to tissue hypoxia. Yet, there are myriad alternative mechanisms for

    Department of Emergency Medicine, San Antonio Uniformed Services Health Education Consortium, Fort Sam Houston, TX, United States Corresponding author at: MCHE-EMR, 3551 Roger Brooke Dr., Fort Sam

    Houston, TX 78234, United States

    E-mail address: [email protected]

    Chase Donaldson, MD

    Department of Emergency Medicine, William Beaumont Army Medical

    Center, Fort Bliss, TX, United States

    Correspondence / American Journal of Emergency Medicine 35 (2017) 11901206 1193

    James H. Lantry, MD Department of Emergency Medicine, San Antonio Uniformed Services Health Education Consortium, Fort Sam Houston, TX, United States

    26 May 2017


    1. April MD, Donaldson C, Tannenbaum LI, Moore T, Aguirre J, Pingree A, et al. Emergen- cy department septic shock patient mortality with refractory hypotension vs hyperlactatemia: a retrospective cohort study. Am J Emerg Med 2017. http://dx.doi. org/10.1016/j.ajem.2017.04.055.
    2. Andersen LW, Mackenhauer J, Roberts JC, Berg KM, Cocchi MN, Donnino MW. Etiology and therapeutic approach to elevated lactate levels. Mayo Clin Proc 2013;88:1127-40.
    3. Long B, Koyfman A. Ready for prime time? Biomarkers in sepsis. Emerg Med Clin North Am 2017;35:109-22.
    4. April MD, Aguirre J, Tannenbaum LI, Moore T, Pingree A, Thaxton RE, et al. Sepsis clinical criteria in emergency department patients admitted to an intensive care unit: an external validation study of quick sequential organ failure assessment. J Emerg Med 2017;52:622-31.

      Intubation and salicylate overdose

      To The Editor,

      We read with interest the recent paper discussing the use of hemodial- ysis in intubated salicylate-Poisoned patients [1]. While we commend the authors for attempting to refine the indications for hemodialysis in salicy- late poisoning, we wish to emphasize some of the limitations of their retro- spective poison center chart review. Although the authors correctly remind readers of the precarious relationship between pH and brain salicylate con- centrations so elegantly described by Hill in the 1970s [2], their dataset does not provide the requisite blood gas results required to correctly interpret the clinical ramifications of their patients’ salicylate concentrations. Simply put, it is the pH that is critical, not the presence of an endotracheal tube.

      Additionally, they do not provide the clinical indications for intuba- tion. The Extracorporeal Treatments In Poisoning (EXTRIP) workgroup reviewed the entire published literature on extracorporeal therapies for Salicylate poisoning and gave 1D recommendations for hemodialysis to both altered mental status and hypoxia, independent of salicylate concen- tration [3]. Because it is reasonable to assume that altered mental status and/or hypoxia are the major indications for intubation, we conclude that it is quite likely that all of the patients included in the present study were candidates for hemodialysis based on EXTRIP criteria.

      The outcomes of intubated patients with salicylate concentrations above 80 mg/dL cannot be interpreted as an absolute zero survival due to the ab- sence of information on why they were intubated, the timing of their peak salicylate concentration with their acid-base status and ventilatory parame- ters. We are additionally concerned that many patients with concentrations significantly lower than 80 mg/dL who were not dialyzed also died. The lack of pre-defined exclusion criteria and failure to examine patients with serum salicylate concentration lower than 50 mg/dL casts further doubt on the va- lidity of the authors’ inferences. While intubation is likely a marker of other indications for hemodialysis, the greatest concerns in intubated salicylate patients are the risks of peri-intubation hypoventilation and subsequent ventilator-assisted respiratory acidemia [3-5].

      We emphasize that salicylism is a complex problem. Blood concen- trations must be interpreted in the context of pH, kidney function and, critically, the patient’s overall clinical status. The sole reliance on a par- ticular concentration as a trigger to institute hemodialysis will likely fail to identify many patients in need of extracorporeal support.

      Sophie Gosselin, MD

      McGill University Health Centre, Canada

      Josh J. Wang, MD

      McGill University Emergency Medicine Residency Program, Canada

      Eric Villeneuve, PharmD

      McGill University Health Centre, Canada

      David Juurlink, MD, PhD

      University of Toronto, Canada

      Robert S. Hoffman, MD NYU School of Medicine, United States Corresponding author at: 455 First Avenue, Room 123

      New York, NY 10016, United States

      E-mail address: [email protected]


      McCabe DJ, Lu JJ. The association of hemodialysis and survival in intubated salicylatepoisoned patients. Am J Emerg Med 2017 Jun;35(6):899-903.

    5. Hill JB. Salicylate intoxication. N Engl J Med 1973 May 24;288(21):1110-3.
    6. Juurlink DN, Gosselin S, Kielstein JT, Ghannoum M, Lavergne V, Nolin TD, et al. Extra- corporeal treatment for salicylate poisoning: systematic review and recommenda- tions from the EXTRIP Workgroup. Ann Emerg Med 2015 Aug;66(2):165-81.
    7. Stolbach AI, Hoffman RS, Nelson LS. Mechanical ventilation was associated with acidemia in a case series of salicylate-poisoned patients. Acad Emerg Med 2008; 15(9):866-9 Sep.
    8. Shively RM, Hoffman RS, Manini AF. Acute salicylate poisoning: risk factors for severe outcome. Clin Toxicol (Phila) 2017 Mar;55(3):175-80.

      Response to intubation and salicylate overdose

      We would like to thank our colleagues for reading our study [1] and con- tinuing the discussion on this topic. We respond to their concerns below.

      Understanding very well the limitations and paucity of data that are provided retrospectively from poison center charts, our goal was not to “refine the indications for hemodialysis in salicylate poisoning,” but to add additional observations to the literature. We present a total of 56 cases including 15 fatalities. To reemphasize, the purpose of our study was to describe “the impact of hemodialysis on survival rates in salicy- late-poisoned intubated patients as well as to contribute to the surprisingly limited data related to this group of critical patients” [1]. Though we agree with the sentiment of the EXTRIP guidelines, evidence provided by the workgroup for the indications for hemodialysis in the salicylate-toxic pa- tient is level D, the lowest Level of evidence [2]. The pH is one critical factor in these patients and, although mortality was our primary endpoint, we did initially attempt to extract the blood gas data. We found that blood gases, however, were not consistently performed or documented well. We therefore chose to remove this as our secondary endpoint.

      We cannot hope to include the exact reasons patients were intubated as these were cases managed by multiple different providers in different facilities and the indications were not consistently recorded. It is reason- able to believe these patients were likely intubated due to altered mental status or hypoxia but exact information is simply not reliably available. We do not disagree with the EXTRIP workgroup’s recommendations [3] and we encourage continued scholarship in this area.

      We specifically chose to study the group of salicylate-poisoned pa- tients that we considered to be the most severely poisoned and “at- risk” for decompensation, these being mechanically-ventilated patients because of the associated effects on pH from the relative hypoventilation. The same inclusion criteria and Serum salicylate level as in the methods described by Stolbach et al. were used [4]. The serum salicylate concen- tration of 80 mg/dl is arbitrary; this concentration should not be consid- ered an independent indication for hemodialysis. While reporting our

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