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High Dosage of Dextran 70 Is Associated with Severe Bleeding in Patients Admitted to the Intensive Care Unit for Septic Shock

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High Dosage of Dextran 70 Is Associated with Severe Bleeding in Patients Admitted to the Intensive Care Unit for Septic Shock Dan Med J 59/11 November 2012 DANISH MEDICAL JOURNAL 1 High dosage of dextran 70 is associated with severe bleeding in patients admitted to the intensive care unit for septic shock Lisa Nebelin Hvidt & Anders Perner ABSTRACT tages of resuscitation with synthetic colloids versus crys- ORIGINAL INTRODUCTION: Synthetic colloids are frequently used in talloids remain heavily debated. ARTICLE fluid resuscitation of septic patients. Despite this, little is Serious adverse effects of colloids have been re- Department of known about the potential side effects including the risk ported including acute kidney injury (AKI) [4, 5], bleeding Intensive Care, of renal failure and bleeding. As practice has changed, we [6] and increased mortality [7]. The newly published 6S Rigshospitalet performed a before-and-after study of fluid resuscitation trial demonstrated an increased risk of death at 90 days and outcome in patients with septic shock. and an increase in the need for renal replacement ther- Dan Med J 2012;59(11):A4531 MATERIAL AND METHODS: We retrospectively assessed apy when HES 130/0.42 was used in severe sepsis [8]. all adult patients with septic shock admitted to a general Comparable results were observed in a study of HES intensive care unit (ICU) at a tertiary hospital in the years 200/0.5 [4]. 2006 and 2008. Data on patient characteristics, resuscita- Dextran 70 is a synthetic colloid of glucopolysac- tion fluids in the ICU and outcome were collected from charides which is still being used in the resuscitation of electronic databases and patient files. septic patients in Scandinavia, but to a lesser extent RESULTS: A total of 332 patients with septic shock were in- than other colloid solutions [9]. Dextran 70, however, is cluded: 171 in 2006 and 161 in 2008. The use of mainly largely unstudied in adult patients with sepsis. dextran 70 in 2006 (median 3.5 (interquartile range 1.9-7.1) With a view to collecting data on any side effects of versus 1.5 (0.5-3.0) l, p < 0.0001; 44 (24-86) versus 18 (8-42) ml/kg, p < 0.0001) had changed to mainly crystalloids (Ring- dextran 70, we performed a retrospective study on fluid er’s lactate 0 (0.0-0.3) versus 1.1 (0.0-3.0) l, p < 0.0001) and administration and outcome in patients with septic shock albumin (5%, 0.0 (0.0-1.0) versus 0.8 (0.0-1.5) l, p < 0.0001; in two time periods. We assumed that the use of colloids 20%, 0.0 (0.0-0.3) versus 0.1 (0.0-0.4) l, p < 0.0001) in 2008. was likely to have changed between the two years, and There were no differences in rates of renal replacement our hypothesis was that this might be associated with therapy or 90-day mortality, but more patients experienced differences in AKI rates, bleeding and mortality. severe bleeding in 2006 than in 2008 (30 versus 19%, p = 0.03). Also more red blood cells, plasma and platelets were MATERIAL AND METHODS given in 2006 than in 2008 (p < 0.01 for all). Retrospective data were collected on all adult (aged CONCLUSION: In patients with septic shock, fluid treatment more than 18 years) patients with septic shock admitted had changed from mainly dextran 70 in 2006 to crystalloids to the general Intensive Care Unit (ICU), Rigshospitalet, and albumin in 2008. The administration of high-dosage in 2006 and 2008. dextran 70 was associated with more patients experiencing Patients were identified from the Unit’s clinical and severe bleeding. administrative database (Critical Information System FUNDING: not relevant. (CIS) Daintel, Copenhagen), where data were entered TRIAL REGISTRATION: not relevant. prospectively by the treating intensivist. Inclusion criteria were "diagnostic code septic shock" and "admission date > 31.12.2005 < 01.01.2007" In severe sepsis, fluid resuscitation is essential for re- or "admission date > 31.12.2007 < 01.01.2009". All pa- storing the circulating blood volume and avoiding sepsis- tients below the age of 18 years were excluded. related organ failure and death. The present guidelines for management of patients Basic characteristics with severe sepsis and circulatory failure recommend Baseline characteristics were registered including age, fluid resuscitation with either natural or synthetic col- gender, weight, type of admission (surgical/medical), loids or crystalloids [1]. Simplified Acute Physiology Score (SAPS) II, the max- There is no evidence to support one type of fluid imum Sequential Organ Failure Assessment (SOFA-max) over another [2, 3], and the advantages and disadvan- score during ICU admission, and if the patient had hae- 2 DANISH MEDICAL JOURNAL Dan Med J 59/11 November 2012 Complications and outcome TABLE 1 The use of acute renal replacement therapy (RRT) in the Characteristics of intensive care unit patients with septic shock. ICU was regiw stered from procedure coding (CIS) and by electronic search in the patient files (CIS). Patients 2006 2008 (N = 171) (N = 161) p-value who had received any form of RRT at another hospital or Age, median (25-75 percentiles), years 62 (52-71) 63 (56-72) 0.30 department before ICU admission were not included. Gender, F/M, n 57/104 57/114 0.73 Patients with one or more major bleeding events Body weight, median (25-75 percentiles), kg 80 (70-90) 75 (60-90) 0.10 were included. Major bleeding events were defined as a Surgical admission, n/N (%) 105/171 (61) 86/161 (53) 0.14 minimum of one day of administered erythrocyte sus- SAPS II, median (25-75 percentiles) 56 (43-68)a 51 (41-62)b 0.04 pension in saline with adenine, glucose and mannitol SOFA-max in ICU, median (25-75 percentiles) 12 (10-16)a 12 (10-16)b 0.50 (SAGM) exceeding three units (> 735 ml) AND clinical Haematological malignancy, n/N (%) 29/171 (17%) 22/161 (14%) 0.41 Time in the ICU, median (25-75 percentiles), days 9 (5-17) 8 (4-13) 0.02 bleeding reported in patient files [8]. Time in shock in the ICUc, median (25-75 percentiles), days 4 (2-7) 4 (2-8) 0.51 Mortality rates during ICU admission and at 90 days F = female; ICU = intensive care unit; M = male; SAPS II = Simplified Acute Physiology Score II; were collected from the Danish hospital admission data- SOFA-max = Maximum Sequential Organ Failure Assessment. base (GS Open). a) n = 165; b) n = 147; c) Registered as days of vasopressor therapy with infusion of either noradrena- lin, adrenalin or dopamine. Statistics Frequencies were reported as percentages and differ- ences were tested with Fisher’s exact test. Numerical TABLE 2 values were reported as medians with 25th and 75th percentiles and analysed using the Mann Whitney U Cumulative doses of 2006 2008 resuscitation fluids and (n = 171) (n = 161) p-value test. p values < 0.05 were considered statistically signifi- blood products given Resuscitation fluids cant. All statistical analyses were performed with Graph- to intensive care unit patients with septic Total volume, l 6.12 (3.3-10.7) 5.90 (3.2-10.3) 0.67 Pad Prism 5 for Windows. shock. The values are NaCl 0.9%, l 1.0 (0.1-2.5) 1.0 (0.0-3.0) 0.79 medians (25-75 percen- Ringer’s lactate, l 0.0 (0.0-0.3) 1.1 (0.0-3.0) < 0.0001 Trial registration: not relevant. tiles). Dextran 70 6%, l 3.5 (1.9-7.1) 1.5 (0.5-3.0) < 0.0001 Dextran 70 6%, ml/kg 44 (24-86) 18 (8-42) < 0.0001 RESULTS HES 130/0.4, l 0.0 (0.0-0.0) 0.0 (0.0-0.0) 0.23 HA 5%, l 0.0 (0.0-1.0) 0.8 (0.0-1.5) < 0.0001 A total of 361 patients were registered with septic shock HA 20%, l 0.0 (0.0-0.2) 0.1 (0.0-0.4) < 0.0001 in 2006 and 2008. Blood products Twenty-nine patients were excluded; three patients SAGM, l 2.0 (0.6-4.7) 0.8 (0.3-2.3) < 0.0001 received no vasopressor therapy, and the ICU charts of FFP, l 1.1 (0-2.4) 0.0 (0-0.5) 0.003 26 patients were missing. Patients for whom only few TC, l 0.7 (0-2.3) 0.0 (0-1.3) 0.01 data were missing were included in the analyses: for 11 FFP = fresh-frozen plasma; HA = human albumin; HES = hydroxyethyl starch; SAGM = erythrocyte suspension in saline with adenine, glucose patients data corresponding to a single day were miss- and mannitol; TC = thrombocyte concentrate. ing, for two patients missing data for two days were missing, and for another two patients data correspond- ing to more than two days were missing. Thus, 332 pa- tients were included in the analyses: 171 in 2006 and matological malignancy. Length of shock and number of 161 in 2008. ICU days were collected from patient files. Days of shock The SAPS II and SOFA-max scores could not be de- were defined as days during which vasopressor therapy scribed for six patients in 2006 and for 14 patients in was needed as registered infusion of noradrenalin, 2008 because they had been admitted to the ICU for less adrenalin or dopamine. This definition was used for than 24 hours. practical reasons even though it does not adhere fully to Most patient characteristics did not differ between the international definition of shock. the two years, but SAPS II and days in ICU were higher in Thus, patients with septic shock were identified 2006 than in 2008 (Table 1).
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