Urgent Chemotherapy for Life-Threatening Complications Related to Solid Neoplasms.

OBJECTIVES: Solid neoplasms can be directly responsible for organ failures at the time of diagnosis or relapse. The management of such specific complications relies on urgent chemotherapy and eventual instrumental or surgical procedures, combined with advanced life support. We conducted a multicenter study to address the prognosis of this condition. DESIGN: A multicenter retrospective (2001-2015) chart review. SETTING: Medical and respiratory ICUs. PATIENTS: Adult patients who received urgent chemotherapy in the ICU for organ failure related to solid neoplasms were included. The modalities of chemotherapy, requirements of adjuvant instrumental or surgical procedures, and organ supports were collected. Endpoints were short- and long-term survival rates. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-six patients were included. Lung cancer was the most common malignancy distributed into small cell lung cancer (n = 57) and non-small cell lung cancer (n = 33). The main reason for ICU admission was acute respiratory failure in 111 patients (81.6%), of whom 89 required invasive mechanical ventilation. Compression and tissue infiltration by tumor cells were the leading mechanisms resulting in organ involvement in 78 (57.4%) and 47 (34.6%) patients. The overall in-ICU, in-hospital, 6-month, and 1-year mortality rates were 37%, 58%, 74%, and 88%, respectively. Small cell lung cancer was identified as an independent predictor of hospital survival. However, this gain in survival was not sustained since the 1-year survival rates of small cell lung cancer, non-small cell lung cancer, and non-lung cancer patients all dropped below 20%. CONCLUSIONS: Urgent chemotherapy along with aggressive management of organ failures in the ICU can be lifesaving in very selected cancer patients, most especially with small cell lung cancer, although the long-term survival is hardly sustainable.

"It Was the Only Thing I Could Hold Onto, But ": Receiving a Letter of Condolence After Loss of a Loved One in the ICU: A Qualitative Study of Bereaved Relatives' Experience.

OBJECTIVES: Family members of patients who die in the ICU often remain with unanswered questions and suffer from lack of closure. A letter of condolence may help bereaved relatives, but little is known about their experience of receiving such a letter. The objective of the study was to understand bereaved family members' experience of receiving a letter of condolence. DESIGN: Qualitative study using interviews with bereaved family members who received a letter of condolence and letters written by these family members to the ICU team. This study was designed to provide insight into the results of a larger randomized, controlled, multicenter study. SETTING: Twenty-two ICUs in France. SUBJECTS: Family members who lost a loved one in the ICU and who received a letter of condolence. MEASUREMENTS AND MAIN RESULTS: Thematic analysis was used and was based on 52 interviews and 26 letters. Six themes emerged: 1) a feeling of support, 2) humanization of the medical system, 3) an opportunity for reflection, 4) an opportunity to describe their loved one, 5) continuity and closure, and 6) doubts and ambivalence. Possible difficulties emerged, notably the re-experience of the trauma, highlighting the absence of further support. CONCLUSIONS: This study describes the benefits of receiving a letter of condolence; mainly, it humanizes the medical institution (feeling of support, confirmation of the role played by the relative, supplemental information). However, this study also shows a common ambivalence about the letter of condolence's benefit. Healthcare workers must strive to adapt bereavement follow-up to each individual situation.

Acetaminophen-Induced Changes in Systemic Blood Pressure in Critically Ill Patients: Results of a Multicenter Cohort Study.

OBJECTIVES: We sought to assess the incidence of acetaminophen-induced hypotension. Our secondary objectives were to describe systemic hemodynamic changes and factors associated with this complication. DESIGN: Prospective observational study. SETTING: Three ICUs. PATIENTS: Adult patients requiring IV acetaminophen infusion. Arterial pressure was monitored via an arterial catheter for 3 hours. Hypotension was defined as a decrease in the mean arterial pressure of greater than or equal to 15% compared with the baseline. RESULTS: Overall, 160 patients were included in this study. Eighty-three patients (51.9%) experienced acetaminophen-induced hypotension according to our definition. In patients with acetaminophen-induced hypotension, the nadir mean arterial pressure was 64 mm Hg (95% CI, 54-74). Hypotension was observed 30 minutes (95% CI, 15-71) after acetaminophen infusion. Changes in mean arterial pressure were closely correlated with decreases in the diastolic arterial pressure (r = 0.92) and to a lesser extent with changes in the pulse pressure (r = 0.18) and heart rate (r = 0.09). Changes in the body temperature were not correlated with changes in mean arterial pressure (r = 0.0002; p = 0.85). None of the patients' baseline characteristics (shock, use of angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, lactates, renal replacement therapy, chronic heart disease, and indication for acetaminophen infusion) or clinically relevant characteristics (baseline severity according to Logistic Organ Dysfunction score, need for vasopressors, use of antihypertensive agents, need for mechanical ventilation, or changes in the body temperature) were independently associated with acetaminophen-induced hypotension. Among patients with acetaminophen-induced hypotension, 29 (34.9%) required therapeutic intervention. CONCLUSIONS: Half of the patients who received IV injections of acetaminophen developed hypotension, and up to one third of the observed episodes necessitated therapeutic intervention. Adequately powered randomized studies are needed to confirm our findings, provide an accurate estimation of the consequences of acetaminophen-induced hypotension, and assess the pathophysiologic mechanisms involved.

Effect of Acetazolamide vs Placebo on Duration of Invasive Mechanical Ventilation Among Patients With Chronic Obstructive Pulmonary Disease: A Randomized Clinical Trial.

IMPORTANCE: Acetazolamide has been used for decades as a respiratory stimulant for patients with chronic obstructive pulmonary disease (COPD) and metabolic alkalosis, but no large randomized placebo-controlled trial is available to confirm this approach. OBJECTIVE: To determine whether acetazolamide reduces mechanical ventilation duration in critically ill patients with COPD and metabolic alkalosis. DESIGN, SETTING, AND PARTICIPANTS: The DIABOLO study, a randomized, double-blind, multicenter trial, was conducted from October 2011 through July 2014 in 15 intensive care units (ICUs) in France. A total of 382 patients with COPD who were expected to receive mechanical ventilation for more 24 hours were randomized to the acetazolamide or placebo group and 380 were included in an intention-to treat analysis. INTERVENTIONS: Acetazolamide (500-1000 mg, twice daily) vs placebo administered intravenously in cases of pure or mixed metabolic alkalosis, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days. MAIN OUTCOMES AND MEASURES: The primary outcome was the duration of invasive mechanical ventilation via endotracheal intubation or tracheotomy. Secondary outcomes included changes in arterial blood gas and respiratory parameters, weaning duration, adverse events, use of noninvasive ventilation after extubation, successful weaning, the duration of ICU stay, and in-ICU mortality. RESULTS: Among 382 randomized patients, 380 (mean age, 69 years; 272 men [71.6%]; 379 [99.7%] with endotracheal intubation) completed the study. For the acetazolamide group (n = 187), compared with the placebo group (n = 193), no significant between-group differences were found for median duration of mechanical ventilation (-16.0 hours; 95% CI, -36.5 to 4.0 hours; P = .17), duration of weaning off mechanical ventilation (-0.9 hours; 95% CI, -4.3 to 1.3 hours; P = .36), daily changes of minute-ventilation (-0.0 L/min; 95% CI, -0.2 to 0.2 L/min; P = .72), or partial carbon-dioxide pressure in arterial blood (-0.3 mm Hg; 95% CI, -0.8 to 0.2 mm Hg; P = .25), although daily changes of serum bicarbonate (between-group difference, -0.8 mEq/L; 95% CI, -1.2 to -0.5 mEq/L; P < .001) and number of days with metabolic alkalosis (between-group difference, -1; 95% CI, -2 to -1 days; P < .001) decreased significantly more in the acetazolamide group. Other secondary outcomes also did not differ significantly between groups. CONCLUSIONS AND RELEVANCE: Among patients with COPD receiving invasive mechanical ventilation, the use of acetazolamide, compared with placebo, did not result in a statistically significant reduction in the duration of invasive mechanical ventilation. However, the magnitude of the difference was clinically important, and it is possible that the study was underpowered to establish statistical significance. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01627639.

Handgrip strength to predict extubation outcome: a prospective multicenter trial.

BACKGROUND: ICU-acquired weakness (ICUAW) has been shown to be associated with prolonged duration of mechanical ventilation and extubation failure. It is usually assessed through Medical Research Council (MRC) score, a time-consuming score performed by physiotherapists. Handgrip strength (HG) can be monitored very easily at the bedside. It has been shown to be a reproducible and reliable marker of global muscular strength in critical care patients. We sought to test if muscular weakness, as assessed by handgrip strength, was associated with extubation outcome. METHODS: Prospective multicenter trial over an 18 months period in six mixed ICUs. Adults receiving mechanical ventilation for at least 48 h were eligible. Just before weaning trial, HG, Maximal Inspiratory Pressure (MIP), Peak Cough Expiratory Flow (PCEF) and Medical Research Council (MRC) score were registered. The attending physicians were unaware of the tests results and weaning procedures were conducted according to guidelines. Occurrence of unscheduled reintubation, non-invasive ventilation (NIV) or high-flow nasal continuous oxygen (HFNC) because of respiratory failure within 7 days after extubation defined extubation failure. The main outcome was the link between HG and extubation outcome. RESULTS: 233 patients were included. Extubation failure occurred in 51 (22.5%) patients, 39 (17.2%) required reintubation. Handgrip strength was 12 [6-20] kg and 12 [8-20] kg, respectively, in extubation success and failure (p = 0.85). There was no association between extubation outcome and MRC score, MIP or PCEF. Handgrip strength was well correlated with MRC score (r = 0.718, p < 0.0001). ICU and hospital length of stay were significantly higher in the subset of patients harboring muscular weakness as defined by handgrip performed at the first weaning trial (respectively, 15 [10-25] days vs. 11 [7-17] days, p = 0.001 and 34 [19-66] days vs. 22 [15-43] days, p = 0.002). CONCLUSION: No association was found between handgrip strength and extubation outcome. Whether this was explained by the appropriateness of the tool in this specific setting, or by the precise impact of ICUAW on extubation outcome deserves to be further evaluated. Trial registration Clinical Trials; NCT02946502, 10/27/2016, URL: https://clinicaltrials.gov/ct2/results?cond=&term=gripwean&cntry=&state=&city=&dist=.

Increased intensity of treatment and decreased mortality in elderly patients in an intensive care unit over a decade.

OBJECTIVES: Data collected from two cohorts of patients aged > or =80 yrs and admitted to an intensive care unit in France were compared to determine whether intensive care unit care and survival had evolved from the 1990s to the 2000s. DESIGN: Retrospective cohort study on patient data attained during intensive care unit stays. SETTING: 18-bed intensive care unit in an academic medical center. PATIENTS: Two cohorts of patients aged > or =80 yrs, admitted to an intensive care unit at a 10-yr interval. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The first cohort comprised 348 patients admitted between January 1992 and December 1995, and the second cohort, 373 patients admitted between January 2001 and December 2004. There was no difference in age between the two cohorts, but patients in the second had significantly less history of functional limitation and significantly more acute illness (Simplified Acute Physiology Score II 43 +/- 18 vs. 57 +/- 25, respectively, p < .0001). Patients in the second cohort had a significantly higher Omega Score, had a higher occurrence of renal replacement therapy, and received vasopressors more frequently than the patients in the first cohort, even when adjusted for age, sex, Knaus classification, Simplified Acute Physiology Score II, and intensive care unit admission cause. Intensive care unit mortality was 65% and 64% for the first and second cohorts, respectively. In multivariate analysis (including age, Knaus classification, Simplified Acute Physiology Score II and first vs. second period) for association with intensive care unit survival, the 2001-2004 period was associated with a near tripling of chances of survival (odds ratio 2.9; 95% confidence interval, 1.92-4.47, p < .0001). CONCLUSIONS: The characteristics and intensity of treatment for elderly people admitted to the intensive care unit changed significantly over a decade. The intensity of treatments has increased over time and survival has improved over time as well. A potential link between increased treatment and improved survival in the elderly may be evoked.

A comparative study of the protein C pathway in septic and nonseptic patients with organ failure.

RATIONALE: Severe sepsis is associated with an exacerbated procoagulant state with protein C (PC) system impairment. In contrast, the inflammatory and coagulation status of nonseptic patients with organ failure (OF) is less documented. OBJECTIVES: To compare coagulation activation, focusing on the PC system, and inflammatory status in septic and nonseptic patients with OF. METHODS: Thirty patients with severe sepsis and 30 nonseptic patients were recruited at the onset of OF and compared with 30 matched healthy subjects. We performed an extensive analysis of the PC pathway, including plasma protein measurements and quantification of leukocyte expression of PC system receptors. In addition, we analyzed the inflammatory status, based on inflammation-related gene leukocyte expression. MEASUREMENTS AND MAIN RESULTS: We observed coagulation activation, reflected by a similar increase in tissue factor mRNA expression, in the two patient groups when compared with the healthy subjects. Soluble thrombomodulin levels were higher in septic patients than in healthy control subjects, whereas PC, protein S, and soluble endothelial cell PC receptor levels were lower. Similar results were obtained in nonseptic patients with OF. Monocyte thrombomodulin overexpression, together with increased circulating levels of activated PC, suggests that the capacity for PC activation is at least partly preserved in both settings. No difference in the inflammatory profile was found between septic and nonseptic patients. CONCLUSIONS: The pathogenesis of OF in critical care patients is characterized by an overwhelming systemic inflammatory response and by exacerbated coagulation activation, independently of whether or not infection is the triggering event. Clinical trial registered with www.clinicaltrials.gov (NCT 00361725).

Effect of a condolence letter on grief symptoms among relatives of patients who died in the ICU: a randomized clinical trial.

PURPOSE: Family members of patients who die in the intensive care unit (ICU) may experience symptoms of stress, anxiety, depression, posttraumatic stress disorder (PTSD), and/or prolonged grief. We evaluated whether grief symptoms were alleviated if the physician and the nurse in charge at the time of death sent the closest relative a handwritten condolence letter. METHODS: Multicenter randomized trial conducted among 242 relatives of patients who died at 22 ICUs in France between December 2014 and October 2015. Relatives were randomly assigned to receiving (n = 123) or not receiving (n = 119) a condolence letter. The primary endpoint was the Hospital Anxiety and Depression Score (HADS) at 1 month. Secondary endpoints included HADS, complicated grief (ICG), and PTSD-related symptoms (IES-R) at 6 months. Observers were blinded to group allocation. RESULTS: At 1 month, 208 (85.9%) relatives completed the HADS; median score was 16 [IQR, 10-22] with and 14 [8-21.5] without the letter (P = 0.36). Although scores were higher in the intervention group, there were no significant differences regarding the HADS-depression subscale (8 [4-12] vs. 6 [2-12], mean difference 1.1 [-0.5 to 2.6]; P = 0.09) and prevalence of depression symptoms (56.0 vs. 42.4%, RR 0.76 [0.57-1.00]; P = 0.05). At 6 months, 190 (78.5%) relatives were interviewed. The intervention significantly increased the HADS (13 [7-19] vs. 10 [4-17.5], P = 0.04), HADS-depression subscale (6 [2-10] vs. 3 [1-9], P = 0.02), prevalence of depression symptoms (36.6 vs. 24.7%, P = 0.05) and PTSD-related symptoms (52.4 vs. 37.1%, P = 0.03). CONCLUSIONS: In relatives of patients who died in the ICU, a condolence letter failed to alleviate grief symptoms and may have worsened depression and PTSD-related symptoms. Trial registration Clinicaltrials.gov Identifier: NCT02325297.

Renal failure in septic shock: predictive value of Doppler-based renal arterial resistive index.

OBJECTIVE: Because acute renal failure (ARF) is frequent in septic shock, an early marker of ARF could impact on management of such patients. High renal arterial resistive index (RI) is associated with parenchymatous renal failure. We assessed whether Doppler-measured RI on day 1 (D1) of septic shock can predict ARF. DESIGN: Prospective descriptive clinical study. SETTING: A 20-bed medical intensive care unit in a university hospital. PATIENTS: All patients with septic shock, excluding those with chronic renal failure (serum creatinine >120 micromol/l). MEASUREMENTS AND RESULTS: RI was determined during the first 24 h (D1) following vasopressor introduction, concomitant with recording of: age, SAPS II, mean arterial pressure, arterial lactate, catecholamine (dose and type), urine output and serum creatinine. ARF was diagnosed according to the RIFLE classification. RI measurement was possible for 35 of 37 included patients. On day 5 (D5), 17 patients were without ARF (RIFLE-0 or R) and 18 patients were classified as having ARF (RIFLE-I or F). On D1, RI was higher in these latter 18 patients (0.77+/-0.08 vs. 0.68+/-0.08, p<0.001). They also had higher SAPS II and arterial lactate concentration. RI >0.74 on D1 had a positive likelihood ratio of 3.3 (95% CI 1.1-35) for developing ARF on D5. RI correlated inversely with mean arterial pressure (rho=-0.48, p=0.006) but not with catecholamine type or dose or with lactate concentration. CONCLUSION: Doppler-based determination of RI on D1 in septic shock patients may help identify those who will develop ARF.

Elevated growth-arrest-specific protein 6 plasma levels in patients with severe sepsis.

OBJECTIVE: Growth-arrest-specific protein 6 (Gas6), an intracellular protein released by apoptotic cells, has been detected in normal plasma. As the Gas6 system has been implicated in mouse susceptibility to sepsis, and as leukocyte apoptosis is thought to play a major role in the physiopathology of human severe sepsis, we studied Gas6 plasma levels and possibly related variables in patients with severe sepsis. DESIGN: Matched case-control study. SETTING: Adult intensive care unit in a university hospital. PATIENTS: Thirty patients with severe sepsis, 30 patients with organ failure not related to infection, and 30 healthy subjects matched for age and gender. INTERVENTIONS: Blood draw. MEASUREMENTS AND MAIN RESULTS: Gas6 plasma levels were quantified using enzyme-linked immunosorbent assay. Whole-blood gas6 messenger RNA levels were measured by quantitative real-time polymerase chain reaction. Gas6 plasma levels were elevated (110 ng/mL [75, 139]; median values [interquartile range]) in severe sepsis patients compared with organ failure patients (85 ng/mL [56, 101]) and healthy subjects (54 ng/mL [49, 68]). In patients with severe sepsis, this increase correlated with the Acute Physiology and Chronic Health Evaluation II severity score, the organ failure Organ Dysfunction and Infection (ODIN) score, and the existence of a septic shock. Gas6 messenger RNA levels were increased in patients with severe sepsis and correlated specifically with the monocyte count. CONCLUSIONS: In severe sepsis, the recently described anti-apoptotic protein Gas6 was found at high levels in plasma and correlated well with the degree of organ dysfunction.