Outcomes in adult critically Ill cancer patients with and without neutropenia: a systematic review and meta-analysis of the Groupe de Recherche en Réanimation Respiratoire du patient d'Onco-Hématologie (GRRR-OH)

Abstract

PURPOSEWhether neutropenia has an impact on the mortality of critically ill cancer patients remains controversial, yet it is widely used as an admission criterion and prognostic factor.METHODSSystematic review and meta-analysis. Studies on adult cancer patients and intensive care units were searched on PubMed and Cochrane databases (2005-2015). Summary estimates of mortality risk differences were calculated using the random-effects model.RESULTSAmong the 1,528 citations identified, 38 studies reporting on 6,054 patients (2,097 neutropenic patients) were included. Median mortality across the studies was 54% [45–64], with unadjusted mortality in neutropenic and non-neutropenic critically ill patients of 60% [53–74] and 47% [41–68], respectively. Overall, neutropenia was associated with a 10% increased mortality risk (6%-14%; I2 = 50%). The admission period was not associated with how neutropenia affected mortality. Mortality significantly dropped throughout the study decade [−11% (−13.5 to −8.4)]. This mortality drop was observed in non-neutropenic patients [−12.1% (−15.2 to −9.0)] but not in neutropenic patients [−3.8% (−8.1 to +5.6)].Sensitivity analyses disclosed no differences in underlying malignancy, mechanical ventilation use, or Granulocyte-colony stimulating factor use. Seven studies allowed the adjustment of severity results (1,350 patients). Although pooled risk difference estimates were similar to non-adjusted results, there was no significant impact of neutropenia on mortality (risk difference of mortality, 9%; 95% CI, −15 to +33)CONCLUSIONAlthough the unadjusted mortality of neutropenic patients was 11% higher, this effect disappeared when adjusted for severity. Therefore, when cancer patients become critically ill, neutropenia cannot be considered as a decision-making criterion.

The prognostic impact of abdominal surgery in cancer patients with neutropenic enterocolitis: a systematic review and meta-analysis, on behalf the Groupe de Recherche en Réanimation Respiratoire du patient d’Onco-Hématologie (GRRR-OH)

“…Patients should be carefully monitored using repeated imaging to assess bowel wall thickness in addition to clinical response, as relapses can occur [ 61 ]. We found that the protective association of abdominal surgery with outcome tended to decrease over time compared to conservative treatment, probably because major advances have been made in the last decade in the medical management of severe sepsis and septic shock [ 19 , 20 ], management of onco-hematology patients including in the ICU setting [ 21 , 62 ] and including neutropenic patients [ 12 , 22 ] and organ failures management [ 24 – 27 ]. Interestingly, surgery did not become deleterious, whereas medical management improved.…”

“…Major advances have been made in the last decade in onco-hematology patients, particularly in the management of septic shock [ 19 , 20 ], critically ill onco-hematology patients admitted to the intensive care unit (ICU) [ 21 ], neutropenic cancer patients [ 12 , 22 ] and organ failures including acute respiratory failure [ 23 – 27 ]. Surprisingly, no major improvements have been reported in neutropenic cancer patients presenting with surgical acute abdominal syndrome [ 28 ].…”

“…Nevertheless, no published studies comforted this idea. Moreover, neutropenia is not considered anymore as an unfavorable prognostic factor in critically ill cancer patients, as recently published in a large meta-analysis [ 22 ]. Surgery even appeared to be associated with a good prognosis in a recent publication in neutropenic cancer patients with acute abdominal pain [ 12 ].…”

Influence of neutropenia on mortality of critically ill cancer patients: results of a meta-analysis on individual data

“…The lack of prognostic impact in critically ill cancer patients may thus reflect an absence of statistical power or the influence of coexistent mechanisms of immune deficiency in these patients. In a previous systematic review performed on aggregated data, neutropenia was associated with an increase in relative risk of death of 10% in critically ill cancer patients [ 17 ]. With regards to the limited number of studies reporting an adjusted impact of neutropenia, however, this preliminary study failed to demonstrate an independent impact of neutropenia on outcome [ 17 ].…”

Short‐ and long‐term outcomes of neutropenic cancer patients in intensive care according to requirement for invasive ventilation

“…In several recent studies, neutropenia had been recognised as having no significant mortality effect among cancer patients admitted to ICU, and this has led to society guidelines recommending against the use of neutropenia as a triage criterion . However, a meta‐analysis of available studies on neutropenic critically ill cancer patients, published in 2018 by Georges et al ., found that neutropenia was independently associated with poor outcome, and thus should be considered during prognostication.…”