piperidines and Critical-Illness

To critically evaluate the use of analgosedation in the management of agitation in critically ill mechanically ventilated patients.. Literature was accessed through MEDLINE (1948-November 2011) and Cochrane Library (2011, issue 1) using the terms analgosedation, analgosedation, or analgesia-based sedation alone or in combination with intensive care unit or critically ill. Reference lists of related publications were also reviewed.. All articles published in English were evaluated. Randomized controlled trials examining critically ill mechanically ventilated patients older than 18 years were included.. Limitations of current sedation practices include serious adverse drug events, prolonged mechanical ventilation time, and intensive care unit (ICU) length of stay. Studies have demonstrated that analgosedation, a strategy that manages patient pain and discomfort first, before providing sedative therapy, results in improved patient outcomes compared to standard sedative-hypnotic regimens. Nine randomized controlled trials comparing remifentanil-based analgosedation to other commonly used agents (fentanyl, midazolam, morphine, and propofol) for ICU sedation and 1 trial comparing morphine to daily sedation interruption with propofol or midazolam were reviewed. Remifentanil is an ideal agent for analgosedation due to its easy titratability and organ-independent metabolism. When compared to sedative-hypnotic regimens, remifentanil-based regimens were associated with shorter duration of mechanical ventilation, more rapid weaning from the ventilator, and shorter ICU length of stay. Compared to fentanyl-based regimens, remifentanil had similar efficacy with the exception of increased pain requirements upon remifentanil discontinuation. Analgosedation was well tolerated, with no significant differences in hemodynamic stability compared to sedative-hypnotic regimens.. Analgosedation is an efficacious and well-tolerated approach to management of ICU sedation with improved patient outcomes compared to sedative-hypnotic approaches. Additional well-designed trials are warranted to clarify the role of analgosedation in the management of ICU sedation, including trials with nonopioid analgesics.

Topics: Analgesia; Analgesics; Critical Illness; Humans; Hypnotics and Sedatives; Intensive Care Units; Length of Stay; Piperidines; Randomized Controlled Trials as Topic; Remifentanil; Respiration, Artificial; Treatment Outcome

Cognitive impairment occurs in up to one-third of intensive care patients and may affect one or more cognitive domains. Because data are scarce on therapies for this complication, prevention remains the prevailing strategy. In this review, we discuss the clinical approach to cognitive impairment after an intensive care unit (ICU) stay.

Topics: Cholinesterase Inhibitors; Cognition; Cognition Disorders; Cognitive Behavioral Therapy; Critical Illness; Donepezil; Dopamine Uptake Inhibitors; Humans; Indans; Intensive Care Units; Methylphenidate; Piperidines; Psychometrics; Survivors

This meta-analysis examined the benefits of using remifentanil as a sedative agent in critically ill patients. A total of 11 randomised controlled trials, comparing remifentanil with another opioid or hypnotic agent in 1067 critically ill adult patients, were identified from the Cochrane controlled trials register and EMBASE and MEDLINE databases, and subjected to meta-analysis. Remifentanil was associated with a reduction in the time to tracheal extubation after cessation of sedation (weighted-mean-difference -2.04 h (95% CI -0.39 to -3.69 h); p = 0.02). Remifentanil was, however, not associated with a significant reduction in mortality (relative risk 1.01 (95% CI 0.67-1.52); p = 0.96), duration of mechanical ventilation, length of intensive care unit stay, and risk of agitation (relative risk 1.08 (95% CI 0.64-1.82); p = 0.77) when compared to an alternative sedative or analgesic agent. The current evidence does not support the routine use of remifentanil as a sedative agent in critically ill adult patients.

Topics: Adult; Conscious Sedation; Critical Illness; Humans; Hypnotics and Sedatives; Piperidines; Randomized Controlled Trials as Topic; Remifentanil

Remifentanil has been proposed as the most suitable systemic opioid for use in obstetrics. Although the onset and offset are rapid, it cannot achieve maximum effect within the time period of a single uterine contraction. Nevertheless, it provides worthwhile analgesia mainly for the first stage of labor with consistently high maternal satisfaction. Maternal oxygen desaturation limits the dose and suitable monitoring during use is advised. As an adjunct to general anesthesia, it is successful in blunting responses to airway manipulation and providing hemodynamic stability in high-risk women. Neonatal effects when used in labor are minimal, but when combined with general anesthesia neonatal depression is unpredictable and more likely with an infusion dose greater than 0.1 microg/kg/min.

Topics: Adult; Analgesia, Obstetrical; Anesthesia, Epidural; Anesthesia, Obstetrical; Anesthetics, Combined; Anesthetics, Intravenous; Cesarean Section; Critical Illness; Female; Humans; Infant, Newborn; Nitrous Oxide; Oxygen; Piperidines; Pregnancy; Remifentanil

Intolerance of enteral feeding due to impaired gastrointestinal motility is common in critically ill patients. Strategies to prevent or treat gastrointestinal hypomotility include the use of prokinetic agents. Many currently employed prokinetic agents are associated with serious adverse drug reactions. The novel prokinetic agents - alvimopan, tegaserod, and dexloxiglumide - are reviewed.. Alvimopan exerts mixed, but generally favorable, effects on restoration of gastrointestinal motility in patients with postoperative ileus. The observation of increased opioid requirements (without increased pain scores) and associated clinical ramifications requires further study. Tegaserod stimulates the peristaltic reflex and improves motility in multiple sites along the gastrointestinal tract. Its efficacy in improving gastrointestinal hypomotility in the critically ill population has not yet been determined. Furthermore, its use has been associated with the development of ischemic colitis and increased requirement for abdominal/pelvic surgery. Dexloxiglumide may be beneficial for improving gastric emptying in critically ill patients, especially those receiving lipid-enriched enteral feeds.. Novel prokinetic agents show promise for management of gastrointestinal hypomotility in the critically ill population. However, further study is required before these agents can be recommended for use.

Topics: Adult; Critical Illness; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Indoles; Pentanoic Acids; Piperidines

Several advances are likely to benefit the ICU patient requiring sedation, analgesia, and anxiolysis. The cooperative sedation induced by dexmedetomidine is a unique and valuable state that allows patients to be aroused easily and interferes little with ventilation. Remifentanil is the prototype of short-acting drugs, providing fast onset and offset; its relatively high cost may be balanced by limiting the risk for long-lasting respiratory depression. Lorazepam seems to be finding more proponents, especially in long-term ICU sedation where the costs of the newer agents may be prohibitive.

Topics: Adrenergic alpha-Agonists; Anti-Anxiety Agents; Critical Illness; Dexmedetomidine; Humans; Hypnotics and Sedatives; Intensive Care Units; Lorazepam; Piperidines; Receptors, Adrenergic, alpha; Remifentanil

Previous studies have shown a beneficial effect of curcuminoids supplementation on serum concentrations of adipokines; however, there are no published studies that have examined this effect among critically ill patients. We aimed to assess the effects of supplementation with curcuminoids on serum concentrations of leptin and adiponectin in critically ill patients with traumatic brain injury (TBI). In this trial, 62 critically ill patients with TBI, aged 18-65 years, were randomly allocated to receive either 500 mg/day curcuminoids (co-administered with 5 mg/day piperine) or matched placebo for 7 days. Patients in both intervention groups received routine treatments for TBI as well as enteral nutrition. Serum concentrations of leptin and adiponectin were measured at baseline and at the end of trial. We found a significant reduction in serum levels of leptin in both curcuminoids (47.1%) and placebo (22.8%) groups; though the magnitude of reduction was greater in the former (p < .05). Supplementation with curcumioinds was not found to alter serum concentrations of adiponectin (p > .05). Supplementation with curcumioinds significantly reduced serum levels of leptin but had no significant effect on adiponectin levels in critically ill patients with TBI. Further clinical trials, particularly those with a long-term period, are needed to confirm our findings.

Topics: Adipokines; Adiponectin; Adolescent; Adult; Aged; Alkaloids; Benzodioxoles; Critical Illness; Curcumin; Diarylheptanoids; Dietary Supplements; Double-Blind Method; Female; Humans; Iran; Leptin; Male; Middle Aged; Piperidines; Placebos; Polyunsaturated Alkamides; Young Adult

Camicinal is a novel, nonmacrolide, motilin receptor agonist that accelerates gastric emptying in critically ill patients with established feed intolerance. The primary question was whether the preemptive administration of camicinal increased the provision of enteral nutrition (EN) to critically ill patients with risk factors that predisposed to feed intolerance.. This was an international, multicenter, parallel-group, blinded, randomized controlled trial. Patients at risk for feed intolerance, defined as receiving moderate to high doses of vasopressors or opiates, or admitted because of multiple traumatic injuries or with brain injury, received either enteral camicinal 50 mg or placebo daily for a maximum of 7 days, along with EN administered according to a standardized feeding protocol. The primary outcome was the daily adequacy of enteral feed delivered, as assessed by percentage of goal volume (delivered/prescribed × 100) before development of intolerance.. Eighty-four patients participated. The administration of camicinal did not result in a statistically significant clinical difference in the daily average percentage goal volume delivered (camicinal vs placebo: 77% [95% confidence interval: 71, 83] vs 68% (58, 78); mean difference 9% [-5, 23]; P = 0.21). Similarly, there were no differences in the percentage goal calories (76% [65, 88] vs 68% [60, 77]) and protein (76% [66, 86] vs 70% [61, 80]) administered, or the incidence of feed intolerance (15% vs 14%).. The incidence of feed intolerance was low in both groups. In this cohort the preemptive administration of enteral camicinal did not significantly augment the provision of goal EN.

Topics: Adult; Aged; Critical Illness; Dietary Proteins; Double-Blind Method; Energy Intake; Enteral Nutrition; Female; Food Intolerance; Gastric Emptying; Humans; Intubation, Gastrointestinal; Male; Middle Aged; Nutritional Requirements; Piperazines; Piperidines; Placebos; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Risk Factors; Treatment Outcome

To investigate the influence of analgesic-based midazolam sedation on delirium and outcomes in critically ill patients and to analyze the risk factors of delirium.. Single center, prospective randomized controlled trial.. A surgical intensive care unit (ICU) in a tertiary care hospital in China.. Mechanically ventilated patients requiring sedation.. Patients admitted to the surgical intensive care unit who required sedation and were undergoing mechanical ventilation for longer than 24 hours were randomly divided into three groups: 1) the remifentanil group received remifentanil and midazolam, 2) the fentanyl group received fentanyl and midazolam, and 3) the control group received only midazolam. The analgesic effect, sedation depth, and presence of delirium were evaluated. To compare the effect of different therapies on the occurrence of delirium, days of mechanical ventilation, length of the ICU stay, and 28-day mortality were measured along with the risk factors for delirium. A total of 105 patients were enrolled, and 35 patients were included in each group. Compared to the control group, patients who received remifentanil and fentanyl required less midazolam each day (P = 0.038 and <0.001, respectively). Remifentanil has a significant effect on reducing the occurrence of delirium (P = 0.007). The logistic regression analysis of delirium demonstrated that remifentanil (OR 0.230, 95%Cl 0.074-0.711, P = 0.011) is independent protective factors for delirium, and high APACHE II score (OR 1.103, 95%Cl 1.007-1.208, P = 0.036) is the independent risk factor for delirium.. Remifentanil and fentanyl can reduce the amount of midazolam required, and remifentanil could further reduce the occurrence of delirium.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Critical Illness; Deep Sedation; Emergence Delirium; Female; Fentanyl; Humans; Male; Midazolam; Middle Aged; Piperidines; Remifentanil; Respiration, Artificial; Time Factors

The promotility agents currently available to treat gastroparesis and feed intolerance in the critically ill are limited by adverse effects. The aim of this study was to assess the pharmacodynamic effects and pharmacokinetics of single doses of the novel gastric promotility agent motilin agonist camicinal (GSK962040) in critically ill feed-intolerant patients.. A prospective, randomized, double-blind, parallel-group, placebo-controlled, study was performed in mechanically ventilated feed-intolerant patients [median age 55 (19-84), 73 % male, APACHE II score 18 (5-37) with a gastric residual volume ≥200 mL]. Gastric emptying and glucose absorption were measured both pre- and post-treatment after intragastric administration of 50 mg (n = 15) camicinal and placebo (n = 8) using the (13)C-octanoic acid breath test (BTt1/2), acetaminophen concentrations, and 3-O-methyl glucose concentrations respectively.. Following 50 mg enteral camicinal, there was a trend to accelerated gastric emptying [adjusted geometric means: pre-treatment BTt1/2 117 minutes vs. post- treatment 76 minutes; 95 % confidence intervals (CI; 0.39, 1.08) and increased glucose absorption (AUC240min pre-treatment: 28.63 mmol.min/L vs. post-treatment: 71.63 mmol.min/L; 95 % CI (1.68, 3.72)]. When two patients who did not have detectable plasma concentrations of camicinal were excluded from analysis, camicinal accelerated gastric emptying (adjusted geometric means: pre-treatment BTt1/2 121 minutes vs. post-treatment 65 minutes 95 % CI (0.32, 0.91) and increased glucose absorption (AUC240min pre-treatment: 33.04 mmol.min/L vs. post-treatment: 74.59 mmol.min/L; 95 % CI (1.478, 3.449). In those patients receiving placebo gastric emptying was similar pre- and post-treatment.. When absorbed, a single enteral dose of camicinal (50 mg) accelerates gastric emptying and increases glucose absorption in feed-intolerant critically ill patients.. The study protocol was registered with the US NIH clinicaltrials.gov on 23 December 2009 (Identifier NCT01039805 ).

Topics: Adult; Aged; Aged, 80 and over; Critical Illness; Double-Blind Method; Enteral Nutrition; Feeding and Eating Disorders; Female; Gastric Absorption; Gastric Emptying; Gastrointestinal Motility; Glucose; Humans; Intensive Care Units; Male; Middle Aged; Piperazines; Piperidines; Placebos; Prospective Studies; South Australia

To investigate the influence of the midazolam sedation based on remifentanil analgesia on the occurrence of delirium in critically ill patients in intensive care unit (ICU).. A single-center prospective randomized controlled trial was conducted. 140 consecutive critically ill patients admitted to ICU of Peking University People's Hospital, undergoing mechanical ventilation longer than 24 hours, with the need of sedation, from February 2014 to January 2015 were enrolled. They were randomly divided into two groups by computer generated random numbers table, each n = 70. The patients in observation group received midazolam 1 μg x kg(-1) x min(-1) for sedation, and 1 mg/mL remifentanil for analgesia with 0.05 mg/kg intravenous bolus, then continuous infusion of 0.02-0.10 mg x kg(-1) x h(-1). The patients in control group received midazolam for sedation only. The data were recorded as follows: the main indices for observation included the occurrence of delirium and its duration; the second item for observation was consumption of drug for sedation, followed by the mean arterial pressure (MAP) before and after sedation, the time of wake-up, duration of mechanical ventilation, the length of ICU stay, and 28-day fatality rate. The 28-day survival was analyzed by Kaplan-Meier survival curve.. The dosage of remifentanil used in observation group was (98.6 ± 24.9) mg/d, the dosage of midazolam was significantly lower than that of the control group (mg/d: 160.6 ± 33.3 vs. 178.9 ± 43.4, t = 2.829, P = 0.005), the incidence of delirium was obviously lower than that of the control group [22.9% (16/70) vs. 57.1% (40/70), χ2 = 15.700, P < 0.001], and the time of delirium was slightly shorter than that of the control group (hours: 162.9 ± 78.0 vs. 194.8 ± 117.3, t = 0.947, P = 0.348). Among the patients with delirium, the dosage of dexmedetomidine used in observation group was significantly less than that of the control group (mg/d: 0.54 ± 0.11 vs. 0.64 ± 0.14, t = 2.112, P = 0.041). The MAP before sedation was similar as the MAP after sedation in both groups, and there was no significant difference between observation group and control group [mmHg (1 mmHg = 0.133 kPa), before treatment: 84.7 ± 16.2 vs. 89.5 ± 37.7, after treatment: 82.3 ± 10.7 vs. 80.8 ± 13.9, both P > 0.05]. There was no significant difference in the time of waking-up between observation group and control group (hours: 2.3 ± 0.9 vs. 2.4 ± 0.8, t = 0.487, P = 0.627). The duration of mechanical ventilation (hours: 143.4? 138.3 vs. 163.9? 158.9, t = 0.812, P = 0.418), the length of ICU stay (days: 8.8 ± 7.7 vs. 10.0 ± 7.8, t = 0.917, P = 0.361) and 28-day fatality rate [11.4% (8/70) vs. 20.0% (14/70), χ2 = 1.941, P = 0.245] in observation group were slightly lower than those of the control group without significant difference. Kaplan-Meier survival curve showed that the cumulative 28-day survival rate in observation group was slightly higher than that of control group (χ2 = 1.647, P = 0.199) CONCLUSION: Analgesia based on sedation may reduce the occurrence of delirium and its severity, furthermore, even if delirium occurs, it may be less severe.

Topics: Analgesia; Arterial Pressure; Critical Illness; Delirium; Dexmedetomidine; Humans; Hypnotics and Sedatives; Intensive Care Units; Kaplan-Meier Estimate; Midazolam; Pain; Piperidines; Prospective Studies; Remifentanil; Respiration, Artificial

To compare automated administration of propofol and remifentanil guided by the Bispectral index (BIS) versus manual administration of short-acting drugs in critical care patients requiring deep sedation. The primary outcome was the percentage of BIS values between 40 and 60 (BIS(40-60)).. This randomized controlled phase II trial in the intensive care unit (ICU) was conducted in adults with multiorgan failure. Thirty-one patients were assigned to receive sedation with propofol or remifentanil either by an automated or a manual system, both targeting BIS(40-60). Performance and feasibility of an automated administration were assessed.. The study groups were well balanced in terms of demographic characteristics. Study duration averaged 18 [8-24] h in the automated group and 14 [9-21] h in the manual group (p = 0.81). Adequate sedation (BIS(40-60)) was significantly more frequent in the automated group 77 [59-82] % than in the manual group 36 [22-56] %, with p = 0.001. Propofol consumption was reduced by a factor of 2 in the automated group with a median change of infusion rates of 39 ± 9 times per hour. In contrast, there were only 2 ± 1 propofol and 1 ± 1 remifentanil dose changes per hour in the manual group compared to 40 ± 9 for remifentanil in the automated group (p < 0.001). Vasopressors were more often discontinued or reduced in the automated group than in the manual control group (36 [6-40] vs. 12 [4-20] modifications, p = 0.03).. Continuous titration of propofol and remifentanil sedation with an automatic controller maintains deep sedation better than manual control in severely ill patients. It is associated with reduced sedative and vasopressor use.

Topics: Adult; Aged; Algorithms; Anesthetics, Intravenous; Automation; Critical Illness; Deep Sedation; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Piperidines; Propofol; Prospective Studies; Remifentanil; Single-Blind Method

This article is a report of a study conducted to determine if a nursing-implemented protocol of daily interruption of sedative infusions vs. sedation as directed by the intensive care unit team would decrease duration of mechanical ventilation.. Continuous rather than intermittent infusion of sedative and analgesic agents leads to greater stability in sedation level, but has been correlated with prolongation of mechanical ventilation and hospitalization of critical care patients. Daily interruption of sedative infusions in mechanically ventilated patients has reduced the duration of mechanical ventilation and length of stay in intensive care.. A randomized controlled trial was carried out from November 2004 to March 2006 with 97 patients receiving mechanical ventilation and continuous infusion of sedative drugs in an intensive care unit in Greece. The primary outcome measure was the duration of mechanical ventilation. Secondary outcomes were length of intensive care unit stay, length of hospital stay, overall mortality, total doses of sedative and analgesic medicines and Ramsay scores and duration of cessation of sedative infusions per day.. The median duration of mechanical ventilation was 8.7 days vs. 7.7 days (P = 0.7). Length of intensive care unit stay (median: 14 vs. 12, P = 0.5) and in the hospital (median: 31 vs. 21, P = 0.1) was similar between the intervention and control groups. The absence of statistically significant differences in these variables remained when patients with brain injury were examined separately.. The nursing-implemented protocol of daily interruption of sedative infusions was neither beneficial nor harmful compared with usual practice, which has as its primary target the earliest possible awakening of patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Critical Care; Critical Illness; Female; Humans; Hypnotics and Sedatives; Length of Stay; Male; Middle Aged; Piperidines; Propofol; Remifentanil; Respiration, Artificial; Time Factors; Treatment Outcome; Ventilator Weaning; Young Adult

To investigate glycine and ammonia plasma concentrations during a 72-h remifentanil infusion and the relationship between glycine concentration and remifentanil infusion rate.. A prospective open-label observational clinical trial in a trauma and a neurosurgical intensive care unit in a university teaching hospital.. Nine consecutive patients requiring sedation and ventilatory support for at least 72 h. One was excluded due to acute cardiac failure.. Patients were sedated with remifentanil and propofol. Glycine and ammonia plasma concentrations were measured every 12 h during an intravenous remifentanil infusion performed over 72 h, and 24 h after the end of the infusion. Cumulative remifentanil dose and rate of infusion were recorded for each patient. Clinical and biological signs of glycine toxicity were evaluated.. Glycine and ammonia plasma concentrations did not exceed the toxic threshold at any time. Plasma glycine concentration measured at the end of remifentanil infusion was significantly correlated with the mean weighted rate of remifentanil infusion and with the cumulative remifentanil dose. A correlation between plasma glycine concentration and creatinine clearance at the end of remifentanil infusion was also documented.. Plasma glycine concentration was correlated with the remifentanil cumulative dose and the infusion rate and did not reach the toxic threshold. As glycine concentration was also correlated with creatinine clearance and because remifentanil was the only source of exogenous glycine, additional data are necessary to ascertain the safety of remifentanil infusion in ICU patients.

Topics: Adult; Ammonia; Creatinine; Critical Illness; Female; Glycine; Humans; Hypnotics and Sedatives; Infusions, Intravenous; Male; Middle Aged; Piperidines; Propofol; Prospective Studies; Remifentanil

It was the aim of this investigation to report our initial clinical experience on the use of remifentanil in critically ill patients undergoing mechanical ventilation. Additionally, we hypothesized that even under intensive care conditions remifentanil might facilitate a temporally predictable and "programmed" tracheal extubation.. Remifentanil was used for analgesia and sedation of mechanically ventilated patients who were admitted to the ICU following major noncardiac surgery or who had to be ventilated due to respiratory failure. The infusion was started with 0.15 microg/kg/min and then adapted in steps of 0.05 microg/kg/min according to clinical needs. After admission to the ICU the depth of sedation was adjusted to a Ramsay score level of 4 (sleeping patient, immediately arousable) and then targeted at a level of 2-3 (patient awake, co-operative and tranquil or responding to command only). In case of sufficient pain relief but inadequate sedation patients could receive bolus doses of midazolam (1-3 mg) or an infusion of clonidine (0.5 microg/kg/h), the latter especially in case of shivering or hypertension. Prior to extubation bolus doses of piritramide (3-5 mg) and a non-opioid analgesic (metamizol or propacetamol) could be used for postoperative pain relief. Data are presented as mean+/-SD.. A total of 46 patients were studied, aged 62.8+/-15.4 yr with a mean APACHE II score of 19.2 points. The duration of remifentanil infusion ranged up to 78 h with a mean of 9. 8 h. The mean infusion rate was 0.14+/-0.08 microg/kg/min during ongoing analgesia and sedation and 0.10+/-0.08 microg/kg/min immediately before its discontinuance. Additional sedatives were necessary in 63% of all patients. Emergence was rapid in the majority of cases: 67% of all patients could safely be extubated within 15 min after termination of remifentanil, and a total of 87% were extubated within 45 min. A development of tolerance was not observed during the study period.. Remifentanil appeared to be suitable for analgesia and sedation of critically ill patients undergoing mechanical ventilation: Even under intensive care conditions recovery was rapid in the majority of cases, and in two thirds of all patients tracheal extubation was temporally predictable and could be timed within 15 min. These results are best explained by the metabolism and offset of action of remifentanil obviously unaffected in the ICU area. However, for fast emergence the cautious use of additional sedatives is crucial.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; APACHE; Critical Illness; Female; Humans; Hypnotics and Sedatives; Intubation, Intratracheal; Male; Middle Aged; Piperidines; Postoperative Period; Remifentanil; Respiration, Artificial; Respiratory Mechanics; Time Factors

To investigate the absorption of the gastrokinetic drug, cisapride, and effect of cisapride on gastric emptying in critically ill patients; and to assess the usefulness of clinical signs of gastric emptying.. Prospective, randomized, controlled study.. Medical/surgical/trauma intensive care unit (ICU) in a university hospital.. Twenty-seven consecutively enrolled patients, aged 18 to 65 yrs, with normal hepatic and renal biochemistry who were not receiving enteral nutrition and who had no contraindications to enteral nutrition. These patients were expected to stay in the ICU for at least 4 days.. Patients were randomized to receive either placebo or rectal cisapride, 60 mg initially followed by two doses of 30 mg at 8-hr intervals.. Gastric emptying was estimated, using acetaminophen absorption on day 1 of the study. Placebo or cisapride was administered and a second acetaminophen absorption test for gastric emptying was carried out on day 2,24 hrs after the first test. Four patients were excluded because of incomplete data. Statistical analysis was performed, using the area under the acetaminophen absorption curve from 0 to 60 mins as the primary measure of gastric emptying. There was no significant change in the area under the acetaminophen absorption curve from 0 to 60 mins from day 1 to day 2 in patients who received placebo or cisapride. Using the combination of the time to maximum acetaminophen concentration (< or = 30 mins) with a maximum concentration (> 12 mg/L) to define "normal" emptying, on day 1, four of the 11 placebo patients had the "normal" gastric emptying, and by day 2, five patients fulfilled this criterion. Before administration of cisapride, four of the 12 patients fulfilled this criterion, whereas nine fulfilled the criterion after receiving cisapride. There was a large variation in gastric emptying from day 1 to day 2; a power calculation suggests that approximately 150 patients would have to be studied to determine the effect of cisapride. There was no correlation between gastric emptying and the volume of gastric aspirate or the presence of bowel sounds. Plasma cisapride concentrations 4 hrs after the third dose, during the second acetaminophen absorption test, averaged 53 ng/mL (range 20 to 111).. Rectal cisapride in the dose given achieved average plasma concentrations similar to those concentrations achieved in healthy subjects after 30 mg of cisapride rectally. There is a large variation in gastric emptying from one day to the next and large numbers of patients are required to determine if cisapride administration improves early gastric emptying in critically ill patients. The volume of gastric aspirate and the presence of bowel sounds do not correlate with gastric emptying.

Topics: Administration, Rectal; Adolescent; Adult; Aged; Cisapride; Critical Illness; Enteral Nutrition; Female; Gastric Emptying; Humans; Intestinal Absorption; Male; Middle Aged; Parasympathomimetics; Piperidines; Prospective Studies; Time Factors

We conducted a randomized, double-blind, placebo-controlled trial in mechanically ventilated intensive care unit (ICU) patients to evaluate the effect of cisapride on gastric emptying using an acetaminophen absorption model. We enrolled 72 patients expected to remain in the ICU for more than 48 h; 39% were female; the average age was 54.0 +/- 19.1 yr; 47% were postoperative, 83% were receiving narcotics, and the mean simplified acute physiology score (SAPS) was 9.5 +/- 3.0. Within 72 h of admission to ICU, 1.6 g of acetaminophen suspension was administered via a nasogastric tube into the stomach (Day 1). Blood samples were drawn at baseline, 30, 60, 90, 120, and 180 min for measurement of plasma acetaminophen levels. The following morning (Day 2), patients were randomized to receive 20 mg of cisapride or placebo and gastric emptying was again assessed. The difference (Day 2-Day 1) in the maximal plasma concentration was 49.1 mumol/L in the cisapride groups compared with 12.3 mumol/L in the placebo group (p = 0.005) and the time to reach maximal concentration was significantly shorter in the cisapride group (-40.8 min versus -4.2 min, p = 0.02). The difference in area under the time-acetaminophen concentration curve was also greater in the patients receiving cisapride (5,534 versus 2,832, p = 0.09). We conclude that cisapride enhances gastric emptying in critically ill patients. Studies to examine the effect of cisapride on tolerance to enteral nutrition, infectious morbidity, and other clinically important outcomes are warranted.

Topics: Acetaminophen; Anti-Ulcer Agents; Cisapride; Critical Illness; Double-Blind Method; Female; Gastric Emptying; Humans; Male; Middle Aged; Piperidines; Respiration, Artificial; Serotonin Antagonists

To investigate the effect of cisapride, a relatively new prokinetic agent, on gastric emptying in critically ill patients.. Prospective, randomized, controlled study.. Adult medical/surgical intensive care unit in a university hospital.. Twenty-one consecutively enrolled patients, requiring prolonged mechanical ventilation and enteral feeding.. Patients were randomized to receive either no cisapride or 10 mg of cisapride four times daily, which was added to a standard enteral nutrition feeding protocol.. Gastric emptying was evaluated by daily measurements of gastric residue and on days 5 through 7 by bedside scintigraphy. Normal values for gastric clearance of a tracer-labeled test meal and for measurements obtained in the supine position were determined in ten healthy volunteers. The mean time at which 50% of the technetium 99m-labeled test meal was eliminated from the stomach (T 1/2) in this control group was 31 +/- 15 mins. In ten critically ill patients (enteral nutrition group), gastric emptying was markedly delayed after 5 to 7 days of enteral feeding (mean T 1/2 = 78 +/- 40 mins; p < .002 as compared with the control group). In contrast, patients treated with cisapride (cisapride group) showed an accelerated gastric emptying (mean T 1/2 = 18 +/- 7 mins; p > .05 as compared with controls; p < .005 as compared with enteral nutrition group). The mean gastric residue over a 1-wk period was also significantly lower in the cisapride group than in the enteral nutrition group (17.7 +/- 8.9 vs. 94.5 +/- 33.4 mL; p < .001).. The data indicate that gastric emptying in critically ill, sedated, and mechanically ventilated patients can be significantly improved by adding cisapride to a routine enteral feeding protocol.

Topics: Aged; Aged, 80 and over; Anti-Ulcer Agents; Cisapride; Critical Illness; Enteral Nutrition; Female; Gastric Emptying; Humans; Male; Middle Aged; Piperidines; Prospective Studies; Radionuclide Imaging; Stomach

Lung cancer complicated with Trousseau syndrome (TS) or disseminated intravascular coagulation (DIC) has a severe prognosis. We herein report an elderly lung cancer patient who presented with a critically ill condition due to concomitant TS and DIC and responded dramatically to alectinib. There are no rules regarding treatment indications based on the age or severity of critically ill patients. If the patient's cancer cells are positive for anaplastic lymphoma kinase rearrangement, alectinib is worthwhile to administer, even in a critically ill condition. In our patient, anticoagulation failed to suppress the TS complications. We also report how to prevent the recurrence of TS.

Topics: Adenocarcinoma of Lung; Aged; Carbazoles; Critical Illness; Disseminated Intravascular Coagulation; Humans; Lung Neoplasms; Piperidines

Critical illness myopathy (CIM) represents a common consequence of modern intensive care, negatively impacting patient health and significantly increasing health care costs; however, there is no treatment available apart from symptomatic and supportive interventions. The chaperone co-inducer BGP-15 has previously been shown to have a positive effect on the diaphragm in rats exposed to the intensive care unit (ICU) condition. In this study, we aim to explore the effects of BGP-15 on a limb muscle (soleus muscle) in response to the ICU condition.. Sprague-Dawley rats were subjected to the ICU condition for 5, 8 and 10 days and compared with untreated sham-operated controls.. BGP-15 significantly improved soleus muscle fibre force after 5 days exposure to the ICU condition. This improvement was associated with the protection of myosin from post-translational myosin modifications, improved mitochondrial structure/biogenesis and reduced the expression of MuRF1 and Fbxo31 E3 ligases. At longer durations (8 and 10 days), BGP-15 had no protective effect when the hallmark of CIM had become manifest, that is, preferential loss of myosin. Unrelated to the effects on skeletal muscle, BGP-15 had a strong positive effect on survival compared with untreated animals.. BGP-15 treatment improved soleus muscle fibre and motor protein function after 5 days exposure to the ICU condition, but not at longer durations (8 and 10 days) when the preferential loss of myosin was manifest. Thus, long-term CIM interventions targeting limb muscle fibre/myosin force generation capacity need to consider both the post-translational modifications and the loss of myosin.

Topics: Animals; Critical Illness; Disease Models, Animal; Female; Intensive Care Units; Muscle Contraction; Muscle, Skeletal; Muscular Diseases; Oximes; Piperidines; Rats; Rats, Sprague-Dawley

Topics: Animals; Critical Illness; Intensive Care Units; Muscle, Skeletal; Muscular Diseases; Oximes; Piperidines; Rats

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have shown promising clinical activity in the treatment of non-small-cell lung cancer (NSCLC) that harbors ALK rearrangement. The next-generation ALK-TKI, alectinib, has been reported to have potent efficacy in ALK-positive NSCLC patients including on mutations that confer resistance to crizotinib, which was the first ALK-TKI approved for ALK-positive NSCLC. The efficacy and safety of ALK-TKIs, including crizotinib and alectinib, as the first-line treatment in critically ill patients is unclear. We report one ALK-positive NSCLC patient with poor performance status (PS) and disseminated intravascular coagulation because of respiratory failure and multiple metastases, and experienced the rapid and dramatic response to alectinib without adverse events that can lead to discontinuation and dose reduction of the drug. After a couple of months of treatment with alectinib, radiological review indicated a complete response. The present case is the first reported case of rapid and marked response to alectinib in ALK-positive NSCLC patients who had poor PS and severe organ dysfunction, such as disseminated intravascular coagulation. Further investigation of the safety and efficacy of ALK-TKI for ALK-positive NSCLC patients who are critically ill is warranted.

Topics: Adult; Anaplastic Lymphoma Kinase; Carbazoles; Carcinoma, Non-Small-Cell Lung; Critical Illness; Humans; Lung Neoplasms; Male; Piperidines; Protein Kinase Inhibitors; Receptor Protein-Tyrosine Kinases

Flexible fiberoptic bronchoscopy (FFB) is a major diagnostic tool commonly used in intensive care unit (ICU). However, it generates discomfort and pain and can worsen respiratory and/or hemodynamic condition of critically ill patients. Remifentanil is an ultrashort-acting opioid drug that has been shown to provide effective sedation for painful procedures in spontaneous breathing patients. The aim of this study is to evaluate the safety and efficacy of sedation with remifentanil target-controlled infusion (Remi-TCI) in patients with spontaneous ventilation undergoing FFB in ICU.. Monocentric prospective study. All patients received Remi-TCI with initial effect-site target concentration of 2 ng/mL, progressively titrated according to their comfort and sedation. Respiratory and hemodynamic parameters were assessed before, during, and after the procedure, as well as comfort, level of sedation, FFB conditions, and recovery patterns. Global Remi-TCI data and potential complications of the procedure were also recorded.. Fourteen patients were included. FFB was successful in all patients with good conditions (sedation, global comfort, and cough). No severe hemodynamic or respiratory complications occurred during procedure. Maximum target concentration and total dose of remifentanil were 2.5 ng/mL (2-4 ng/mL) and 1.4 μg/kg (0.7-2.4 μg/kg), respectively, over 10 min. Patients reported low level of pain and good satisfaction with the procedure.. FFB under sedation with Remi-TCI seems to be safe and effective in critically ill patients with spontaneous ventilation. Such results could be the first step towards wider use of Remi-TCI in patients experiencing awkward and/or painful procedures in this setting.

Topics: Aged; Analgesics, Opioid; Bronchoscopy; Conscious Sedation; Critical Illness; Female; Hemodynamics; Humans; Intensive Care Units; Male; Middle Aged; Piperidines; Prospective Studies; Remifentanil; Respiration

A critically ill septic patient on haemofiltration for acute renal failure suffered sudden circulatory and respiratory collapse. The cause of the collapse was traced to an interaction between mechanical devices (syringe driver infusion pumps and haemofiltration equipment) connected to two central venous catheters.

Topics: Acute Kidney Injury; Adolescent; Analgesics, Opioid; Critical Illness; Drug Overdose; Equipment Failure; Female; Hemofiltration; Humans; Hypnotics and Sedatives; Infusion Pumps; Piperidines; Propofol; Remifentanil

To study the analgesic and sedative effects of remifentanil in critically-ill patients.. Remifentanil infusion was started at 0.02 microg x kg(-1) x min(-1) in ten mechanically ventilated critically-ill patients, and the infusion rate was increased to 0.05, 0.10, 0.15, 0.20, and 0.25 microg x kg(-1) x min(-1) every 30 min. Basally and 25 min after each increase we measured: the Ramsey sedation score (RSS) and the respiratory response subscore of comfort scale (CSRR); the bispectral index (BIS) before and after lightly touching tracheal mucosa; heart rate and systemic arterial pressure; respiratory variables; plasma epinephrine and norepinephrine levels.. Infusion rates up to 0.05 microg x kg(-1) x min(-1) were effective against agitation and achieved a good degree of adaption to the respirator in all patients (RSS 2 or more and CSRR 3 or less); BIS decreased significantly; respiratory and circulatory variables were unaffected; mean plasma epinephrine levels decreased. At infusion rates higher than 0.05 microg x kg(-1) x min(-1) RSS but not BIS decreased further and patient arousability caused by noxious stimuli was not prevented; respiratory drive suppression occurred at the infusion rates higher than 0.05 microg x kg(-1) x min(-1) in four patients; bradycardia and arterial hypotension was observed in three patients; plasma epinephrine levels decreased significantly, while norepinephrine was unaffected; severe itching was experienced by one patient.. Low doses of remifentanil (up to 0.05 microg x kg(-1) x min(-1)) can be useful in critically-ill patients in order to achieve calm and sedation. Higher doses can inhibit respiratory drive and require controlled mechanical ventilation.

Topics: Aged; Aged, 80 and over; Critical Illness; Dose-Response Relationship, Drug; Epinephrine; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Piperidines; Prospective Studies; Remifentanil; Respiration; Ventilators, Mechanical

Topics: Administration, Rectal; Cisapride; Critical Illness; Gastric Emptying; Humans; Intestinal Absorption; Parasympathomimetics; Piperidines

Topics: Aged; Analgesics, Opioid; Critical Illness; Humans; Male; Physical Therapy Modalities; Piperidines; Remifentanil

Topics: Adult; Analgesics, Opioid; Critical Illness; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Piperidines; Remifentanil; Respiration, Artificial

Topics: Cisapride; Critical Illness; Erythromycin; Gastric Emptying; Gastrointestinal Agents; Humans; Piperidines

Topics: Analgesics, Opioid; Critical Illness; Drug Evaluation; Ethics, Medical; Humans; Piperidines; Remifentanil