Online Letters to the Editor

normal saline could cause dilutional-hyperchloremic acidosis. It should be noted, though, that dilutional-hyperchloremic acidosis is usually moderate and transient, and convincing evidence for clinically relevant adverse effects, for example, on renal function, is lacking (4). In a recent issue of Critical Care Medicine, Raghunathan et al (5) reported on a large retrospective cohort study of over 50,000 patients with sepsis in 360 hospitals in the United States in which they examined the association between choice of crystalloids (normal saline vs balanced salt solutions) and mortality during the resuscitation of critically ill adults with sepsis. Of note, only a minority of patients received balanced salt solutions (6.4%). Receipt of balanced salt solutions was associated with lower in-hospital mortality (19.6% vs 22.8%; relative risk, 0.86; 95% CI, 0.78–0.94). Also, mortality was progressively lower among patients receiving larger proportions of balanced salt solutions. There were no associations with the prevalence of acute renal failure or in-hospital and ICU lengths of stay. As the authors themselves state, their results should be interpreted with caution, as this was not a controlled trial but a retrospective cohort study over many years in many centers. Time could be a confounder: if there was an increase in use of balanced salt solutions over time, it could be that the found association between choice of crystalloids and mortality was affected by the improved outcome of sepsis over recent years (6, 7). The type of physician could be a confounder as well: if physicians who are aware of the importance of using the surviving sepsis campaign bundle are also the ones that prefer balanced salt solutions, it could be that the found association was affected by the improved outcome due to, for example, timely start of antibiotics (8). Let us try to prevent a catastrophe alike with colloid solutions. Balanced salt solutions are only balanced in respect to their salt content—there might, however, be an imbalance between benefit and harm. Indeed, one could argue that excessive administration of balanced salt solutions may result in metabolic alkalosis and hyperlactatemia (with compounded sodium lactate), cardiotoxicity (with acetate), and increased peripheral vascular resistance, heart rates, and as a consequence worsening of organ ischemia (with magnesium). The only solution is a well-powered randomized controlled trial. The intensive care community needs to take its responsibility: tens, if not hundreds, of thousands patients receive fluid resuscitation each year. The study by Raghunathan et al (5) helps in planning and designing such a trial. The author has disclosed that he does not have any potential conflicts of interest. Marcus J. Schultz, MD, PhD, Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

REFERENCES

1. Serpa Neto A, Veelo DP, Peireira VG, et al: Fluid resuscitation with hydroxyethyl starches in patients with sepsis is associated with an increased incidence of acute kidney injury and use of renal replacement therapy: A systematic review and meta-analysis of the literature. J Crit Care 2014; 29:185.e1–185.e7

Critical Care Medicine

2. Haase N, Perner A, Hennings LI, et al: Hydroxyethyl starch 130/0.380.45 versus crystalloid or albumin in patients with sepsis: Systematic review with meta-analysis and trial sequential analysis. BMJ 2013; 346:f839 3. Myburgh JA, Mythen MG: Resuscitation fluids. N Engl J Med 2013; 369:1243–1251 4. Guidet B, Soni N, Della Rocca G, et al: A balanced view of balanced solutions. Crit Care 2010; 14:325 5. Raghunathan K, Shaw A, Nathanson B, et al: Association Between the Choice of IV Crystalloid and In-Hospital Mortality Among Critically Ill Adults With Sepsis. Crit Care Med 2014; 42:1585–1591 6. Bellomo R, Finfer S, Myburgh J: Mortality in patients with hypovolemic shock treated with colloids or crystalloids. JAMA 2014; 311:1067–1068 7. Ferrer R, Artigas A, Levy MM, et al; Edusepsis Study Group: Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA 2008; 299:2294–2303 8. Ferrer R, Martin-Loeches I, Phillips G, et al: Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: Results from a guideline-based performance improvement program. Crit Care Med 2014; 42:1749–1755 DOI: 10.1097/CCM.0000000000000645

The authors reply:

W

e thank Dr. Schultz (1) for his comments on our study (2). We agree with Dr. Schultz that a reason for our study was to seek an alternative to isotonic saline solution during resuscitation in severe sepsis. However, hyperchloremic or “dilutional” metabolic acidosis (attributed to fluid therapy with isotonic saline solution) may be a misnomer. Chloride, unlike lactate, is not a byproduct of metabolism. Furthermore, although hyperchloremia is diagnosed based on an absolute increase in the chloride value, metabolic acidosis results from an increase in chloride relative to sodium and resulting reduction in the plasma strong ion difference. Thus, the chloride value must always be interpreted with the sodium value to diagnose acidosis (3). Also as Dr. Schultz points out, an increase in the use of balanced crystalloids and a decrease in mortality could simply have gone together over time, suggesting an association where none exists. We examined trends in the use of balanced crystalloids over time and found no significant change (Fig. 1, top). Similarly, physicians aware of the “surviving sepsis campaign (SSC)” bundle may have preferred “balanced salt solutions” (4). Adherence to the SSC bundle rather than the use of balanced crystalloids may have improved mortality. Although we could not control for all elements of the SSC bundle, we adjusted for many of the recommendations including total fluid volume administered, central venous and arterial pressure monitoring, use of colloids, use of activated protein C, early red blood cell transfusion (by day 2), and the receipt of steroids by day 2. Although we are not certain how “bundle adherence” changed over time relative to the specialty of the attending physicians, we observed a modest increase in the number of hospitalists treating patients with sepsis when compared with critical care specialists (Fig. 1, bottom). Using a Lin-type sensitivity analysis, we showed that a significant unmeasured confounder would be needed for the observed association between balanced crystalloids and an www.ccmjournal.org

e27

Online Letters to the Editor

in-hospital mortality to be negated (2). Multiple unmeasured confounders may interact to negate the observed association in our nonexperimental study (including variable timing of antibiotics, use of dynamic hemodynamic monitoring, etc.). Although the “situation remains fluid,” we believe that there is at least consistent circumstantial evidence that the use of balanced crystalloids is associated with improved outcomes among the patients included in our analysis (i.e., among “medically septic” patients treated with vasopressors in an ICU by hospital day 2). Dr. Raghunathan's institution received grant support from Baxter Healthcare USA (investigator-initiated trial award). Dr. Beadles disclosed government work. Dr. Nathanson's institution consulted for OptiStatim, LLC (Dr. Nathanson's company, OptiStatim, LLC, has an ongoing consulting agreement with Duke University School of Medicine to do data analysis and assist in the write-up of academic articles). Dr. Lindenauer has disclosed that he does not have any potential conflicts of interest.

Dr. Beadles was formerly with Health Services Research and Development, Durham VA Medical Center, Durham, NC. Karthik Raghunathan, MD, MPH, Christopher Beadles, MD, PhD, Brian H. Nathanson, PhD, Peter K. Lindenauer, MD, MSc, Division of Veterans Affairs, Department of Anesthesiology, Duke University Medical Center, Durham, NC

REFERENCES

1. Schultz MJ: Balancing Between Benefit and Harm—What Is the Best Solution in Fluid Resuscitation? Crit Care Med 2015; 43:e26–e27 2. Raghunathan K, Shaw A, Nathanson B, et al: Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis*. Crit Care Med 2014; 42:1585–1591 3. Gunnerson KJ: The meaning of acid–base abnormalities in the intensive care unit—epidemiology. Crit Care 2005; 9:508–516 4. Dellinger RP, Levy MM, Carlet JM, et al: International Surviving Sepsis Campaign Guidelines Committee. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36:296–327 DOI: 10.1097/CCM.0000000000000697

Figure 1. Trends in fluid choice and physician specialty: among patients with a diagnosis of sepsis (2005–2010). Top, Crystalloid choice on hospital days 1 and 2 was relatively stable. Exclusively isotonic saline was used for resuscitation in the vast majority of patients. Balanced crystalloids were used, in addition to saline, in 5–6% of the population. Bottom, “Physician mix” changed over time with more “nonspecialists” caring for patients with sepsis.

e28

www.ccmjournal.org

January 2015 • Volume 43 • Number 1

The authors reply.

The authors reply. - PDF Download Free
513KB Sizes 3 Downloads 5 Views