Reducing Mortality in Critically Ill Patients: A Systematic Update


Inclusion criteria

1. Published in peer-reviewed journal

2. Multicenter randomized design

3. Dealt with a nonsurgical intervention (drug/technique/strategy)

4. Involving adult critically ill patients

5. Showing a statistically significant reduction or increase in crude mortality at least at one time point

Exclusion criteria

1. Used a quasi-randomized methodology

2. Dealt with surgical interventions

3. Involved pediatric population

4. Dealt only with the perioperative period

5. Showed a mortality effect only in a subgroup of the studied population

6. Showed a mortality effect only in adjusted mortality analysis


Only four mRCTs that fulfill our inclusion criteria were found. One intervention, hypothermia in bacterial meningitis [7], increased mortality. Three interventions – colloids [8], vasopressin and steroids in cardiocirculatory arrest (CCA) [9], and ulinastatin in severe sepsis [10] – seem to have a beneficial effect on survival. The main characteristics of these trials are summarized in Table 16.2.


Table 16.2
Characteristics of the selected trials











































































 
Intervention

Setting

Effect on survival

No. of centers

No. of patients

RR/OR

p-value

Blinded

Interruption

ITT

Annane D [8]

Colloids

Hypovolemic shock

Increase survival

57

2,857

0.92(0.86–0.99)a

0.03

No

Yes, for futility

Yes

MentzelopoulosS [9]b

Vasopressin+ steroids

In-hospital CCA

Increase survival

3

300

3.28 (1.17–9.29)c

0.02

Yes

No

No

Karnad DR [10]

Ulinastatin (human urinary trypsin inhibitor)

Severe sepsis

Increase survival

7

122

0.26(0.07–0.95)c

0.04

Yes

No

No

Mourvillier B [7]

Hypothermia(32–34 °C for 48 h)

Severe bacterial meningitis

Increase mortality

49

98

1.99(1.05–3.77)a

0.04

No

Yes, for safety

Yes


RR relative risk, OR odd ratio, ITT intention to treat, CCA cardio circulatory arrest

aRR and 95 % confidence interval

bIn this case, the tested outcome is survival with favorable neurological outcome until hospital discharge

cOR and 95 % confidence interval


16.1 Colloids


One large mRCT on the impact of colloids on survival in critically ill patients was published after the Consensus Conference [8]. The CRISTAL trial (Colloids versus Crystalloids for the Resuscitation of the Critically Ill) involved 57 ICUs from five different countries and enrolled 2,857 patients. Patients with hypovolemic shock were randomized to receive fluid resuscitation by either colloid or crystalloids. There was no blinding, and clinicians could choose to administer whichever fluid was available in their institution. Most of the patients in the crystalloid group received normal saline; most of the patients in the colloid group received hydroxyethyl starches. Enrolment was stopped early due to futility at an ad interim analysis; therefore, no significant difference was found in 28-day mortality (primary end point). The need of renal replacement therapy did not differ between the two groups. Ninety-day mortality was investigated as a secondary post hoc endpoint, and a statistical significant difference was found: relative risk (RR) 0.92 (95 % confidence interval (CI) 0.86–0.99), p = 0.03. The authors themselves highlighted the weakness of this result that should be considered as explorative. Nevertheless, this trial started a vivacious debate on the impact of colloids on mortality and on renal impairment. Perner noted that the CRISTAL trial had a high risk of bias, as it was open-label and allocation might have been inadequate [11]. The open-label design imposes to demonstrate equal-quality resuscitation and continuous monitoring of renal function, but both of these points were suboptimal in Annane’s work, according to Bellomo and colleagues [12]. Moreover, the use of different fluids in each intervention group makes the interpretation of these results difficult [11]. The implications of Annane’s work are discussed in Chap. 9, dedicated to the detrimental effect of colloids.


16.2 Vasopressin and Steroids in In-Hospital Cardiac Arrest


Heart diseases still rank as United States first cause of death. Out-of-hospital CCA has an overall incidence of 126 cases per 100,000 inhabitants/year. Survival till hospital discharge is less than 5 % and doubles in case of treatment by the emergency medical services. In case of in-hospital CCA, survival increases up to 24 % [13]. Moreover, among CCA survivors, the prevalence of severe cerebral disability or vegetative state ranges from 25 to 50 %.

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May 9, 2017 | Posted by in CRITICAL CARE | Comments Off on Reducing Mortality in Critically Ill Patients: A Systematic Update

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