Pierre Ingrand

Withholding and withdrawal of life support in intensive-care units in France: a prospective survey

BACKGROUND In France, there are no guidelines available on withholding and withdrawal of life-sustaining treatments, and information on the frequency of such decisions is scarce. METHODS We undertook a prospective 2-month survey in 113, of a total of 220, intensive-care units (ICUs) in France to study the frequency of, and processes leading to, decisions to withhold and withdraw life-sustaining treatments. FINDINGS Life-supporting therapies were withheld or withdrawn in 807 (11.0%) of 7309 patients (withholding in 336 [4.6%] and withdrawal in 471 [6.4%], preceded in 358 by withholding). Of 1175 deaths in ICU, 628 (53%) were preceded by a decision to limit life-supporting therapies. Futility and poor expected quality of life were the most frequently cited reasons. Decisions were strongly correlated with the simplified acute physiological score, but an independent centre effect persisted after adjustment for this score. Decisions were mostly taken by all the ICU medical staff, with (54%) or without (34%) the nursing staff; however, a single physician made decisions in 12% of cases. The patients family was involved in the decision-making process in 44% of cases. The patients willingness to limit his or her own care was known in only 8% of the cases; only 0.5% of the patients were involved in decisions. INTERPRETATION Withholding and withdrawal of life-support therapies are widely practised in French ICUs, despite their prohibition by the French legislation. The lack of an official statement from French scientific bodies may explain several limitations on the various steps of the decision-making process.

Sclerotherapy with or without Octreotide for Acute Variceal Bleeding

BACKGROUND Sclerotherapy is considered the most effective way to stop bleeding from esophageal varices, but acute variceal bleeding is still associated with a high risk of rebleeding and death. We compared sclerotherapy alone with sclerotherapy and octreotide to control acute variceal bleeding and prevent early rebleeding in patients with cirrhosis. METHODS In a double-blind, prospective trial, 199 patients with cirrhosis and acute variceal bleeding who underwent emergency sclerotherapy were randomly assigned to receive a continuous infusion of octreotide (25 micrograms per hour) or placebo for five days. The primary outcome measure was survival without rebleeding five days after sclerotherapy. RESULTS After five days, the proportion of patients who had survived without rebleeding was higher in the octreotide group (85 of 98 patients, or 87 percent) than in the placebo group (72 of 101, or 71 percent; 95 percent confidence interval for the difference, 4 to 27 percent; P = 0.009). The mean number of units of blood transfused within the first 24 hours after sclerotherapy was lower in the octreotide group (1.2 units; range, 0 to 7) than in the placebo group (2.0 units; range, 0 to 10; P = 0.006). A logistic-regression analysis showed that the treatment assignment (P = 0.003) and the number of blood units transfused before any other treatment was undertaken (P = 0.002) were the only two variables independently associated with survival without rebleeding. After adjustment for base-line differences between the two groups, the odds ratio for treatment failure in the placebo group, as compared with the octreotide group, was 3.3 (95 percent confidence interval, 1.5 to 7.3). The mean (+/- SD) 15-day cumulative survival rate (estimated by the Kaplan-Meier method) was 88 +/- 12 percent in both groups. Side effects were minor, and their incidence was similar in the two groups. CONCLUSIONS In patients with cirrhosis, the combination of sclerotherapy and octreotide is more effective than sclerotherapy alone in controlling acute variceal bleeding, but there is no difference between the overall mortality rates associated with the two approaches to treatment.

Functional Recovery and Social Outcome after Cerebral Infarction in Young Adults

This study was designed to assess the return to work, the poststroke depression and the quality of life after a cerebral infarction in young adults and was conducted on 71 consecutive young patients (aged 15–45 years) affected by a cerebral infarct who were hospitalized for the first time and discharged at least 1 year before the study. Data about risk factors, etiology, side and territory of stroke, social characteristics of the patient (age, sex, profession, educational level, family situation), poststroke seizures, recurrent stroke, other vascular events, and deaths were collected. Neurological deficits were graded with the National Institutes of Health (NIH) Stroke Scale. Poststroke depression (PSD) was quantified using the DSM-IIIR criteria and the Montgomery Asberg Depression Rating Scale. Outcomes were rated with the Ranking Scale, the Barthel Index and the Glasgow Outcome Scale. Quality of life was assessed with the Sickness Impact Profile. Follow-up information was obtained by interview and neurological examination. Follow-up information was obtained in 65 patients at a mean of 31.7 ± 13.0 (range 12–59) months, as 2 patients died and 4 were lost to follow-up and were thus excluded from this study. Poststroke seizures occurred in 7 patients (10.8%) and recurrent strokes in 4 patients (6.2%), but none were fatal. The outcome after stroke among survivors was usually good, since more than two-thirds of the patients (69.8%) reported no problem, 11.1% moderate handicap and one-fifth major handicap. Forty-six patients (73%) returned to work; the time period ranging from several days after stroke to 40 months, with a mean of 8 months. However, adjustments in their occupation were necessary for 12 patients (26.1%). PSD was common, since 48.3% of the patients were classified as depressed. PSD was associated with the localization of the infarct (carotid territory), a severe disability, a bad general outcome, and an absence of return to work. Their opinion about their quality of life was negative among approximately 30% of the patients, especially in emotional and alertness behaviors, social interaction, recreation and pastimes.The general outcome after cerebral infarct in young adults is usually good. However, the risk of a PSD is high, and only half of the patients had returned to their previous work. A remaining psychosocial handicap and depression of sexual activity impaired the quality of life. In multivariate analysis, a low NIH score at admission is a significant predictor for return to work, the absence of PSD, and a good quality of life.

Neuropsychological disturbances in cerebellar infarcts.

Background– Recent clinical and research reports suggest that the cerebellum may contribute to the modulation of higher cognitive functions. Material and methods– We included 15 consecutive patients with isolated cerebellar infarcts (4 superior cerebellar artery territory infarcts, 1 anterior inferior cerebellar artery territory infarct and 10 posterior inferior cerebellar artery territory infarcts), all confirmed by magnetic resonance imaging. These subjects plus 15 controls matched for age, sex, and educational level underwent a neuropsychological test battery including vocabulary, similarities and block design subtests of the Wechsler Adult Intelligence Scale Revised (WAIS‐R); verbal fluency tests (categorial, phonemic, and alternate categorial fluency tests); Reys 15 auditory word learning list; the paced auditory serial addition task; the Stroop test and the Zerssen Rating Scale. One year after the cerebellar infarct, each subject with cerebellar infarct was asked to undergo a second neuropsychological examination with the same test battery. Results– Patients with cerebellar infarcts exhibited significantly lower neuropsychological performances compared to those of the control group without any obvious difference between the different vascular cerebellar territories. After 1 year of follow‐up, this neuro‐psychological impairment tended to improve. Conclusions– The pattern of deficits observed in isolated cerebellar infarcts highlights the non‐motor functions of the cerebellum and functional relationship between the cerebral cortex and the cerebellum.

Habitual snoring as a risk factor for brain infarction

The association of habitual snoring with cerebral ischaemia was studied, in a case control‐study, in 133 patients aged 45–75 years (103 men and 30 women) and 133 controls matched for sex and age. Ischaemic stroke was confirmed by brain computed tomography or magnetic resonance imaging. History of risk factors, especially of snoring and sleeping habits was recorded with structured questionnaire during interview. Prevalence of habitual snoring significantly differs between patients with stroke and controls: 31/133 (23.3%) vs 11/133 (8.3%) (Odds ratio 3.4, 95% confidence interval 1.5 to 7.6, p < 0.001). Even after adjusting for matching variables and confounding risk factors (arterial hypertension, cardiac arrhythmia, and obesity), habitual snoring carries a significant risk factor for stroke (odds ratio: 2.9; 95% confidence interval 1.3 to 6.8 (p = 0.01)). The risk of ischaemic stroke was higher among older male patients with arterial hypertension who always snored. Habitual snoring was not significantly linked with sleep‐related stroke nor with the pathophysiology of strokes. Inquiring about habitual snoring should become a routine practice, especially among older male patients with arterial hypertension, and specific preventive measures should be instituted at an earlier stage.

Self‐consciousness and Alzheimer's disease

Objectives– To propose a neuropsychological study of the various aspects of self‐consciousness (SC) in Alzheimers disease. Methods– Forty‐five patients with probable mild or moderate AD were included in the study. Severity of their dementia was assessed by the Mini Mental State (MMS). Fourteen questions were prepared to evaluate SC. Results– No significant correlations were found between SC score and educational level, age, and duration of disease. A significant correlation was found between SC score and the severity of dementia, whereas frontal disturbances were just short of the significance threshold. The various aspects of SC were not impaired to the same degree. The most disturbed ones were awareness of cognitive deficiencies, moral judgements and prospective memory. The least disturbed aspects were awareness of identity and of mental representation of the body. Items relating to anosognosia and moral judgements were significantly correlated with the MMS score, whereas affective state, body representation disorders, prospective memory, and capacities for introspection were not related to the severity of the dementia. Consciousness of identity was sound, regardless of MMS score. Conclusions– AD clearly induces an heterogeneous impairment of SC. SC requires a convergence of many neural networks. In AD, neuronal alterations involve many cortical areas and information sent to the associative frontal cortex from memory, language and visuospatial areas is lacking or disturbed. Thus, the sequential order of successive stimuli cannot be maintained by the heteromodal associative cortex (dorsal convexity of the prefrontal cortex), and the supramodal associative cortex (located rostrally in the frontal lobes) is unable to provide reliable monitoring and assessment of simultaneous neural cognitive networks carrying insufficient and inadequate input. The core deficiency in AD patients might be impaired SC equated with the disability to maintain sequential and simultaneous “attention to life”. The Self‐Consciousness Questionnaire, a clinical scale providing multidimensional measurement, indicates that different aspects of consciousness are not correlated with overall cognitive deficiency as determined by the MMSE.

Is ursodeoxycholic acid an effective therapy for total parenteral nutrition-related liver disease?

Cholestasis is the predominant complication in patients with total parenteral nutrition-related liver disease. Ursodeoxycholic acid has been reported to be beneficial for patients with various chronic cholestatic liver diseases. The aim of this prospective study was to determine the effects of short-term administration of ursodeoxycholic acid in nine patients (mean age 54 years) treated with home total parenteral nutrition (31 +/- 2 (mean +/- SEM) kcal/kg per day) for 13.9 +/- 5.2 months for short bowel syndrome; all presented biological evidence of hepatic cholestasis (mean alkaline phosphatase activity 5.2 times the upper limit of the normal) which appeared during nutrition; there was no cause of hepatic dysfunction other than total parenteral nutrition. Patients received 11.2 +/- 0.8 mg/kg per day of ursodeoxycholic acid orally for 1 (n = 9) or 2 (n = 5) 2-month periods, each of which was followed by a 2-month wash-out period. Liver function tests were performed before and at the end of each period. Compared with non-treatment periods, the two periods of ursodeoxycholic acid administration induced a significant reduction in gamma-glutamyl transpeptidase (27.1% and 20.4% respectively; p = 0.001) and alanine aminotransferase serum activities (7.0% and 34.8% respectively; p = 0.01) from baseline values. Alkaline phosphatase activity (p = 0.09), aspartate aminotransferase (p = 0.11) and bilirubin (p = 0.75) serum activities underwent no significant change during the study. These preliminary results strongly suggest that short-term ursodeoxycholic acid administration leads to biochemical improvement in liver function tests in patients with total parenteral nutrition-related liver disease.

Anti-inflammatory drugs and variceal bleeding: a case-control study

Background Non-steroidal anti-inflammatory drugs (NSAIDs) can have severe gastrointestinal effects and cause peptic ulcers to bleed. Acute bleeding from oesophageal varices is a major complication of cirrhosis of the liver. Aims To investigate the role, using a case-control study, of NSAIDs in first bleeding episodes associated with oesophageal or cardial varices in cirrhotic patients. Patients/Methods A structured interview was conducted of 125 cirrhotic patients with bleeding mainly related to oesophageal varices and 75 cirrhotic controls with oesophageal varices who had never bled. Results Cirrhotic patients who were admitted for bleeding related to portal hypertension were more likely to have used NSAIDs during the week before the index day (31 of 125 (25%)) than the cirrhotic controls (eight of 75 (11%); odds ratio = 2.8, p = 0.016). Use of aspirin alone or combined with other NSAIDs was also more prevalent in the cases (21 of 125 (17%)) than in the controls (three of 75 (4%); odds ratio = 4.9, p = 0.007). Logistic regression analysis showed that NSAID use (p = 0.022, odds ratio = 2.9, 95% confidence interval = 1.8 to 4.7) and variceal size (p<0.001, odds ratio = 4.0, 95% confidence interval = 1.4 to 11.5) were the only variables independently associated with the risk of bleeding. Conclusions Aspirin, used alone or combined with other NSAIDs, was associated with a first variceal bleeding episode in patients with cirrhosis. Given the life threatening nature of this complication, the possible benefit of this treatment should be weighed against the risk shown here. No firm conclusions could be drawn on non-aspirin NSAIDs used alone.

Visual Versus Quantitative Assessment of Intratumor 18F-FDG PET Uptake Heterogeneity: Prognostic Value in Non–Small Cell Lung Cancer

The goal of this study was to compare visual assessment of intratumor 18F-FDG PET uptake distribution with a textural-features (TF) automated quantification and to establish their respective prognostic value in non–small cell lung cancer (NSCLC). Methods: The study retrospectively included 102 consecutive patients. Only primary tumors were considered. Intratumor heterogeneity was visually scored (3-level scale [Hvisu]) by 2 nuclear medicine physicians. Tumor volumes were automatically delineated, and heterogeneity was quantified with TF. Mean and maximum standardized uptake value were also included. Visual interobserver agreement and correlations with quantitative assessment were evaluated using the κ test and Spearman rank (ρ) coefficient, respectively. Association with overall survival and recurrence-free survival was investigated using the Kaplan–Meier method and Cox regression models. Results: Moderate correlations (0.4 < ρ < 0.6) between TF parameters and Hvisu were observed. Interobserver agreement for Hvisu was moderate (κ = 0.64, discrepancies in 27% of the cases). High standardized uptake value, large metabolic volumes, and high heterogeneity according to TF were associated with poorer overall survival and recurrence-free survival and remained an independent prognostic factor of overall survival with respect to clinical variables. Conclusion: Quantification of 18F-FDG uptake heterogeneity in NSCLC through TF was correlated with visual assessment by experts. However, TF also constitutes an objective heterogeneity quantification, with reduced interobserver variability, and independent prognostic value potentially useful for patient stratification and management.

Randomised trial of prevention of biliary stent occlusion by ursodeoxycholic acid plus norfloxacin

Biliary stents are liable to clog. We investigated whether a choleretic plus an antibiotic could delay clogging. 20 consecutive patients with a malignant biliary stricture were randomised after endoscopic insertion of a polyethylene stent to receive ursodeoxycholic acid plus norfloxacin (13-15 mg/kg and 400 mg, daily) or conservative treatment. The drug combination was associated with: a longer median patency of first (49 vs 6 weeks) and all stents (38 vs 7 weeks); a prolonged median survival (67 vs 18 weeks); and a shorter mean hospital stay (0.2 vs 1.0 days per week of survival). Thus ursodeoxycholic acid plus norfloxacin may prevent stent clogging.