Guillaume Thiery

The Prognosis of Acute Respiratory Failure in Critically Ill Cancer Patients

Abstract: Acute respiratory failure (ARF) in patients with cancer is frequently a fatal event. To identify factors associated with survival of cancer patients admitted to an intensive care unit (ICU) for ARF, we conducted a prospective 5-year observational study in a medical ICU in a teaching hospital in Paris, France. The patients were 203 cancer patients with ARF mainly due to infectious pneumonia (58%), but also noninfectious pneumonia (9%), congestive heart failure (12%), and no identifiable cause (21%). We measured clinical characteristics and ICU and hospital mortality rates. ICU mortality was 44.8% and hospital mortality was 47.8%. Noninvasive mechanical ventilation was used in 79 (39%) patients and conventional mechanical ventilation in 114 (56%), the mortality rates being 48.1% and 75.4%, respectively. Among the 14 patients with late noninvasive mechanical ventilation failure (>48 hours), only 1 survived. The mortality rate was 100% in the 19 noncardiac patients in whom conventional mechanical ventilation was started after 72 hours. By multivariable analysis, factors associated with increased mortality were documented invasive aspergillosis (odds ratio [OR], 2.13; 95% confidence intervals [CI], 1.05-14.74), no definite diagnosis (OR, 3.85; 95% CI, 1.26-11.70), vasopressors (OR, 3.19; 95% CI, 1.28-7.95), first-line conventional mechanical ventilation (OR, 8.75; 95% CI, 2.35-35.24), conventional mechanical ventilation after noninvasive mechanical ventilation failure (OR, 17.46; 95% CI, 5.04-60.52), and late noninvasive mechanical ventilation failure (OR, 10.64; 95% CI, 1.05-107.83). Hospital mortality was lower in patients with cardiac pulmonary edema (OR, 0.16; 95% CI, 0.03-0.72). Survival gains achieved in critically ill cancer patients in recent years extend to patients requiring ventilatory assistance. The impact of conventional mechanical ventilation on survival depends on the time from ICU admission to conventional mechanical ventilation and on the patients response to noninvasive mechanical ventilation. Abbreviations: ARDS = acute respiratory distress syndrome, ARF = acute respiratory failure, BAL = bronchoalveolar lavage, HSCT = human stem-cell transplant, ICU = intensive care unit, MV = mechanical ventilation, NIMV = noninvasive mechanical ventilation.

Outcome of Cancer Patients Considered for Intensive Care Unit Admission: A Hospital-Wide Prospective Study

PURPOSE To evaluate the outcome of cancer patients considered for admission to the intensive care unit (ICU). PATIENTS AND METHODS Prospective, one-year hospital-wide study of all cancer and hematology patients, including bone marrow transplantation patients, for whom admission to the ICU was requested. RESULTS Of the 206 patients considered for ICU admission, 105 patients (51%) were admitted. Of the 101 patients who were not admitted, 54 patients (26.2%) were considered too sick to benefit, and 47 patients (22.8%) were considered to be too well to benefit from the ICU. Of these 47 patients, 13 patients were admitted later. Survival rates after 30 and 180 days were significantly associated with admission status (P < .0001). Remission of the malignancy (odds ratio [OR], 3.37; 95% CI, 1.25 to 9.07) was independently associated with ICU admission, whereas poor chronic health status (OR, 0.38; 95% CI, 0.16 to 0.74) and solid tumor (OR, 0.43; 95% CI, 0.24 to 0.78) were associated with ICU refusal. In admitted patients, 30-day and 6-month survival rates were 54.3% and 32.4%, respectively. Of the patients considered too sick to benefit from ICU admission, 26% were alive on day 30 and 16.7% on day 180. Among patients considered too well to benefit, the 30-day survival rate was a worrisome 78.7%. Calibration of the Mortality Probability Model (the only score available at triage) was of limited value for predicting 30-day survival (area under the curve, 0.62). CONCLUSION Both the excess mortality in too-well patients later admitted to the ICU and the relatively good survival in too-sick patients suggest the need for a broader admission policy.

The ICU Trial: A new admission policy for cancer patients requiring mechanical ventilation*

Objective:Cancer patients requiring mechanical ventilation are widely viewed as poor candidates for intensive care unit (ICU) admission. We designed a prospective study evaluating a new admission policy titled The ICU Trial. Design:Prospective study. Setting:Intensive care unit. Patients:One hundred eighty-eight patients requiring mechanical ventilation and having at least one other organ failure. Interventions:Over a 3-yr period, all patients with hematologic malignancies or solid tumors proposed for ICU admission underwent a triage procedure. Bedridden patients and patients in whom palliative care was the only cancer treatment option were not admitted to the ICU. Patients at earliest phase of the malignancy (diagnosis <30 days) were admitted without any restriction. All other patients were prospectively included in The ICU Trial, consisting of a full-code ICU admission followed by reappraisal of the level of care on day 5. Measurements and Main Results:Among the 188 patients, 103 survived the first 4 ICU days and 85 died from the acute illness. Hospital survival was 21.8% overall. Among the 103 survivors on day 5, none of the characteristics of the malignancy were significantly different between the 62 patients who died and the 41 who survived. Time course of organ dysfunction over the first 6 ICU days differed significantly between survivors and nonsurvivors. Organ failure scores were more accurate on day 6 than at admission or on day 3 for predicting survival. All patients who required initiation of mechanical ventilation, vasopressors, or dialysis after 3 days in the ICU died. Conclusions:Survival was 40% in mechanically ventilated cancer patients who survived to day 5 and 21.8% overall. If these results are confirmed in future interventional studies, we recommend ICU admission with full-code management followed by reappraisal on day 6 in all nonbedridden cancer patients for whom lifespan-extending cancer treatment is available.

Outcome of Critically Ill Allogeneic Hematopoietic Stem-Cell Transplantation Recipients: A Reappraisal of Indications for Organ Failure Supports

PURPOSE Because the overall outcome of critically ill hematologic patients has improved, we evaluated the short-term and long-term outcomes of the poor risk subgroup of allogeneic hematopoietic stem-cell transplantation (HSCT) recipients requiring admission to the intensive care unit (ICU). PATIENTS AND METHODS This was a retrospective multicenter study of allogeneic HSCT recipients admitted to the ICU between 1997 and 2003. RESULTS Two hundred nine critically ill allogeneic HSCT recipients were included in the study. Admission in the ICU occurred during the engraftment period (< or = 30 days after transplantation) for 70 of the patients and after the engraftment period for 139 patients. The overall in-ICU, in-hospital, 6-month, and 1-year survival rates were 48.3%, 32.5%, 27.2%, and 21%, respectively. Mechanical ventilation was required in 122 patients and led to a dramatic decrease in survival rates, resulting in in-ICU, in-hospital, 6-month, and 1-year survival rates of 18%, 15.6%, 14%, and 10.6%, respectively. Mechanical ventilation, elevated bilirubin level, and corticosteroid treatment for the indication of active graft-versus-host disease (GVHD) were independent predictors of death in the whole cohort. In the subgroup of patients requiring mechanical ventilation, associated organ failures, such as shock and liver dysfunction, were independent predictors of death. ICU admission during engraftment period was associated with acceptable outcome in mechanically ventilated patients, whereas patients with late complications of HSCT in the setting of active GVHD had a poor outcome. CONCLUSION Extensive unlimited intensive care support is justified for allogeneic HSCT recipients with complications occurring during the engraftment period. Conversely, initiation or maintenance of mechanical ventilation is questionable in the setting of active GVHD.

Predictors of noninvasive ventilation failure in patients with hematologic malignancy and acute respiratory failure

Objectives:The current trend to manage critically ill hematologic patients admitted with acute respiratory failure is to perform noninvasive ventilation to avoid endotracheal intubation. However, failure of noninvasive ventilation may lead to an increased mortality. Design:Retrospective study to determine the frequency of noninvasive ventilation failure and identify its determinants. Setting:Medical intensive care unit in a University hospital. Patients:All consecutive patients with hematologic malignancies admitted to the intensive care unit over a 10-yr period who received noninvasive ventilation. Results:A total of 99 patients were studied. Simplified Acute Physiology Score II at admission was 49 (median, interquartile range, 39–57). Fifty-three patients (54%) failed noninvasive ventilation and required endotracheal intubation. Their Pao2/Fio2 ratio was significantly lower (175 [101–236] vs. 248 [134–337]) and their respiratory rate under noninvasive ventilation was significantly higher (32 breaths/min [30–36] vs. 28 [27–30]). Forty-seven patients (89%) who failed noninvasive ventilation required vasopressors. Hospital mortality was 79% in those who failed noninvasive ventilation, and 41% in those who succeeded. Patients who failed noninvasive ventilation had a significantly longer intensive care unit stay (13 days [8–23] vs. 5 [2–8]) and a significantly higher rate of intensive care unit-acquired infections (32% compared with 7%). Factors independently associated with noninvasive ventilation failure by multivariate analysis were respiratory rate under noninvasive ventilation, longer delay between admission and noninvasive ventilation first use, need for vasopressors or renal replacement therapy, and acute respiratory distress syndrome. Conclusions:Failure of noninvasive ventilation occurs in half the critically ill hematologic patients and is associated with an increased mortality. Predictors of noninvasive ventilation failure might be used to guide decisions regarding intubation.

Determinants of postintensive care unit mortality: a prospective multicenter study.

ObjectiveSix to 25 percent of patients discharged alive from the intensive care unit (ICU) die before hospital discharge. Although this post-ICU mortality may indicate premature discharge from a full ICU or suboptimal management in the ICU or ward, another factor may be discharge from the ICU as part of a decision to limit treatment of hopelessly ill patients. We investigated determinants of post-ICU mortality, with special attention to this factor. DesignProspective, multicenter, database study. SettingSeven ICUs in or near Paris, France. PatientsA total of 1,385 patients who were discharged alive from an ICU after a stay of ≥48 hrs; 150 (10.8%) died before hospital discharge. Decisions to withhold or withdraw life-sustaining treatments were implemented in the ICUs in 80 patients, including 47 (58.7%) who died before hospital discharge. InterventionsNone. Measurements and Main ResultsIn the univariate analysis, post-ICU mortality was associated with advanced age, poor chronic health status, severe comorbidities, severity and organ failure scores (Simplified Acute Physiology Score II, sepsis-related organ failure assessment, and Logistic Organ Dysfunction at admission and at ICU discharge), decisions to withhold or withdraw life-sustaining treatments, and Omega score (reflecting ICU resource utilization and length of ICU stay). Multivariate stepwise logistic regression identified five independent determinants of post-ICU mortality: McCabe class 1 (odds ratio, 0.388 [95% confidence interval, 0.26–0.58]), transfer from a ward (odds ratio, 1.89 [95% confidence interval, 1.27–2.80]), Simplified Acute Physiology Score II score at admission >36 (odds ratio, 1.57 [95% confidence interval, 1.6–2.33]), decisions to withhold or withdraw life-sustaining treatments (odds ratio, 9.64 [95% confidence interval, 5.75–16.6]), and worse sepsis-related organ failure assessment score at discharge (odds ratio, 1.11 [95% confidence interval, 1.03–1.18] per point). ConclusionsMore than 10% of ICU survivors died before hospital discharge. Determinants of post-ICU mortality included variables reflecting patient status before and during the ICU stay. However, the most powerful predictor of post-ICU mortality was the decision to withhold or withdraw life-sustaining treatments in the ICU, suggesting that the decision has been made not to use the unique services of the ICU for these patients.

Clinical review: Specific aspects of acute renal failure in cancer patients

Acute renal failure (ARF) in cancer patients is a dreadful complication that causes substantial morbidity and mortality. Moreover, ARF may preclude optimal cancer treatment by requiring a decrease in chemotherapy dosage or by contraindicating potentially curative treatment. The pathways leading to ARF in cancer patients are common to the development of ARF in other conditions. However, ARF may also develop due to etiologies arising from cancer treatment, such as nephrotoxic chemotherapy agents or the disease itself, including post-renal obstruction, compression or infiltration, and metabolic or immunological mechanisms. This article reviews specific renal disease in cancer patients, providing a comprehensive overview of the causes of ARF in this setting, such as treatment toxicity, acute renal failure in the setting of myeloma or bone marrow transplantation.

Control and Outcome of a Large Outbreak of Colonization and Infection with Glycopeptide- Intermediate Staphylococcus aureus in an Intensive Care Unit

BACKGROUND Glycopeptide-intermediate Staphylococcus aureus (GISA) is emerging as a cause of nosocomial infection and outbreaks of infection and colonization in intensive care units (ICUs). We describe an outbreak of GISA colonization/infection and the ensuing control measures in an ICU and investigate outcomes of the affected patients. METHODS We describe an outbreak of GISA colonization and infection that affected 21 patients in a medical ICU at a tertiary care teaching hospital, as well as the measures taken to eradicate the GISA strain. RESULT Recognition of the outbreak was difficult. Infections, all of which were severe, were diagnosed in 11 of 21 patients. Patient isolation and barrier precautions failed when used alone. Addition of a stringent policy of restricted admissions, twice daily environmental cleaning, and implementation of hand decontamination with a hydroalcoholic solution led to outbreak termination. This was associated with increases in workload, despite a marked decrease in the number of admissions. CONCLUSION This first description of a large outbreak of GISA colonization and infection underlines the importance of routine GISA-strain detection when methicillin-resistant S. aureus is isolated. Outbreak control may be difficult to achieve.

Respiratory status deterioration during G-CSF-induced neutropenia recovery.

Summary:Exacerbation of prior pulmonary involvement may occur during neutropenia recovery. Granulocyte colony-stimulating factor (G-CSF)-related pulmonary toxicity has been documented in cancer patients, and experimental models suggest a role for G-CSF in acute lung injury during neutropenia recovery. We reviewed 20 cases of noncardiac acute respiratory failure during G-CSF-induced neutropenia recovery. Half the patients had received hematopoietic stem cell transplants. All patients experienced pulmonary infiltrates during neutropenia followed by respiratory status deterioration coinciding with neutropenia recovery. Neutropenia duration was 10 (4–22) days, and time between respiratory symptoms and the first day with more than 1000 leukocytes/mm3 was 1 (−0.5 to 2) day. Of the 20 patients, 16 received invasive or noninvasive mechanical ventilation, including 14 patients with acute respiratory distress syndrome (ARDS). Five patients died, with refractory ARDS. In patients with pulmonary infiltrates during neutropenia, G-CSF-induced neutropenia recovery carries a risk of respiratory status deterioration with acute lung injury or ARDS. Clinicians must maintain a high index of suspicion for this diagnosis, which requires eliminating another cause of acute respiratory failure, G-CSF discontinuation and ICU transfer for early supportive management including diagnostic confirmation and noninvasive mechanical ventilation.

Time course of organ dysfunction in thrombotic microangiopathy patients receiving either plasma perfusion or plasma exchange

Introduction:Few studies have investigated adults with thrombotic microangiopathy (TMA) requiring intensive care unit (ICU) admission, and the treatment remains controversial. Objective:To describe causes, outcomes, prognostic factors, and daily organ-failure score changes in adults with TMA requiring ICU admission. Design:A 3-yr single-center cohort study. Patients:The patients were 36 adults with TMA admitted to a teaching-hospital medical ICU between January 2000 and June 2003. Results:Of the 36 patients, 22 received plasma infusion and 15 underwent plasma exchange. All patients had anemia and thrombocytopenia at ICU admission, and 13 had neurologic impairment. Median creatinine clearance was 55.2 mL/min (interquartile range, 28.8–75.4). No patient had congenital TMA. Causative factors included microbiologically documented infection in 14 patients, allogeneic transplantation in 7 patients, and concomitant or subsequent systemic disease in 7 patients; 6 patients were human immunodeficiency virus–positive, 5 had drug-induced TMA, 2 were pregnant, and 2 had cancer. In 10 patients, no causative factors were identified. Plasma exchange was associated with a statistically significant decrease in hospital mortality (0 vs. 7 deaths; p < .001). Moreover, daily organ-failure scores were significantly lower in the plasma-exchange group from day 3 to day 9. Patients in the plasma-exchange group received a larger volume of plasma. Conclusion:Plasma exchange may be associated with faster resolution of organ failure and with improved survival for patients with TMA requiring ICU admission.