Discomfort and factual recollection in intensive care unit patients

INTRODUCTION: A stay in the intensive care unit (ICU), although potentially life-saving, may cause considerable discomfort to patients. However, retrospective assessment of discomfort is difficult because recollection of stressful events may be impaired by sedation and severe illness during the ICU stay. This study addresses the following questions. What is the incidence of discomfort reported by patients recently discharged from an ICU? What were the sources of discomfort reported? What was the degree of factual recollection during patients' stay in the ICU? Finally, was discomfort reported more often in patients with good factual recollection? METHODS: All ICU patients older than 18 years who had needed prolonged (>24 hour) admission with tracheal intubation and mechanical ventilation were consecutively included. Within three days after discharge from the ICU, a structured, in-person interview was conducted with each individual patient. All patients were asked to complete a questionnaire consisting of 14 questions specifically concerning the environment of the ICU they had stayed in. Furthermore, they were asked whether they remembered any discomfort during their stay; if they did then they were asked to specify which sources of discomfort they could recall. A reference group of surgical ward patients, matched by sex and age to the ICU group, was studied to validate the questionnaire. RESULTS: A total of 125 patients discharged from the ICU were included in this study. Data for 123 ICU patients and 48 surgical ward patients were analyzed. The prevalence of recollection of any type of discomfort in the ICU patients was 54% (n = 66). These 66 patients were asked to identify the sources of discomfort, and presence of an endotracheal tube, hallucinations and medical activities were identified as such sources. The median (min–max) score for factual recollection in the ICU patients was 15 (0–28). The median (min–max) score for factual recollection in the reference group was 25 (19–28). Analysis revealed that discomfort was positively related to factual recollection (odds ratio 1.1; P < 0.001), especially discomfort caused by the presence of an endotracheal tube, medical activities and noise. Hallucinations were reported more often with increasing age. Pain as a source of discomfort was predominantly reported by younger patients. CONCLUSION: Among postdischarge ICU patients, 54% recalled discomfort. However, memory was often impaired: the median factual recollection score of ICU patients was significantly lower than that of matched control patients. The presence of an endotracheal tube, hallucinations and medical activities were most frequently reported as sources of discomfort. Patients with a higher factual recollection score were at greater risk for remembering the stressful presence of an endotracheal tube, medical activities and noise. Younger patients were more likely to report pain as a source of discomfort

Influence of pharmacogenetic variability on the pharmacokinetics and toxicity of the aurora kinase inhibitor danusertib

Objectives Danusertib is a serine/threonine kinase inhibitor of multiple kinases, including aurora-A, B, and C. This explorative study aims to identify possible relationships between single nucleotide polymorphisms in genes coding for drug metabolizing enzymes and transporter proteins and clearance of danusertib, to clarify the interpatient variability in exposure. In addition, this study explores the relationship between target receptor polymorphisms and toxicity of danusertib. Methods For associations with clearance, 48 cancer patients treated in a phase I study were analyzed for ABCB1, ABCG2 and FMO3 polymorphisms. Association analyses between neutropenia and drug target receptors, including KDR, RET, FLT3, FLT4, AURKB and AURKA, were performed in 30 patients treated at recommended phase II dose-levels in three danusertib phase I or phase II trials. Results No relationships between danusertib clearance and drug metabolizing enzymes and transporter protein polymorphisms were found. Only, for the one patient with FMO3 18281AA polymorphism, a significantly higher clearance was noticed, compared to patients carrying at least 1 wild type allele. No effect of target receptor genotypes or haplotypes on neutropenia was observed. Conclusions As we did not find any major correlations between pharmacogenetic variability in the studied enzymes and transporters and pharmacokinetics nor toxicity, it is unlikely that danusertib is highly susceptible for pharmacogenetic variation. Therefore, no dosing alterations of danusertib are expected in the future, based on the polymorphisms studied. However, the relationship between FMO3 polymorphisms and clearance of danusertib warrants further research, as we could study only a small group of patients

Probiotics versus antibiotic decontamination of the digestive tract: infection and mortality

Purpose: Selective decontamination of the digestive tract (SDD) has been shown to decrease the infection rate and mortality in intensive care units (ICUs); Lactobacillus plantarum 299/299v plus fibre (LAB) has been used for infection prevention and does not harbour the potential disadvantages of antibiotics. The objective was to assess whether LAB is not inferior to SDD in infection prevention. Methods: Two hundred fifty-four consecutive ICU patients with expected mechanical ventilation ≥48 h and/or expected ICU stay ≥72 h were assigned to receive SDD: four times daily an oral paste (polymyxin E

Renal function in cancer patients treated with hyperthermic isolated limb perfusion with recombinant tumor necrosis factor-α and melphalan

Hyperthermic isolated limb perfusion (HILP) with recombinant tumor necrosis factor-α (r-TNFα) and melphalan has been shown to result in a sepsis-like syndrome due to leakage of r-TNFα from the perfusion system to the systemic circulation. We have studied renal function parameters in 11 cancer patients, who underwent 12 perfusions. Three patients, perfused with melphalan only, served as controls. All patients treated with r-TNFα developed a sepsis syndrome and needed volume replacement and inotropes to remain normotensive; controls had an uneventful postoperative course. Creatinine clearance decreased transiently on the day of perfusion in both groups (mean preperfusion clearance 118 ml/min, mean post-perfusion clearance 68 ml/min, p < 0.02, n = 15). Follow-up measurements of renal plasma flow and glomerular filtration rate in 9 r-TNFα-treated patients did not suggest permanent damage. One patient became hypotensive and developed transient multiple organ dysfunction with renal failure needing hemofiltration. In r-TNFα-treated patients, but not in controls, a transient increase in clearance of β2-microglobulin (0.05 vs. 8 ml/min, p < 0.001) and urinary excretion of phosphate (12 vs. 48 mmol/l, p < 0.05) was seen, compatible with proximal tubular dysfunction. These data suggest that HILP with melphalan decreases glomerular function, whether or not r-TNFα is added to the perfusion circuit. Extension of the treatment regimen with r-TNFα may result in additional proximal tubular dysfunction. If hypotension can be avoided, this deterioration in renal function seems to be transient, with full recovery within weeks

High plasma tumor necrosis factor (TNF)-α concentrations and a sepsis-like syndrome in patients undergoing hyperthermic isolated limb perfusion with recombinant TNF-α, interferon-γ, and melphalan

Objectives: To describe the postoperative course of patients who underwent hyperthermic isolated limb perfusion with recombinant tumor necrosis factor (TNF)-α and melphalan after pretreatment with recombinant interferon-γ as treatment for recurrent melanoma, primary nonresectable soft-tissue tumors, planocellular carcinoma, or metastatic carcinoma. To measure systemic TNF-α concentrations and relate these values with indices of disease severity. Setting: A 12-bed surgical intensive care unit (ICU) in a university referral hospital. Design: Prospective, descriptive study. Patients: Consecutive patients (n = 25) treated with hyperthermic isolated limb perfusion. Interventions: Blood samples were taken at regular intervals to determine TNF-α concentrations during and after hyperthermic isolated limb perfusion with recombinant TNF-α. Hemodynamic variables were obtained with a Swan-Ganz pulmonary artery catheter. Measurements and Main Results: All patients developed features of sepsis syndrome and required intensive care treatment. Most patients recovered quickly, with a median ICU stay of 2 days (range 1 to 25). Maximum systemic TNF-α concentrations ranged from 2284 to 83,000 ng/L (median 25,409) and returned to baseline values within 8 hrs. Despite these high concentrations of TNF-α, no patient died in the ICU, although the patient with the highest TNF-α concentration developed multiple organ failure and required continuous venovenous hemofiltration for 16 days. Linear regression analysis showed positive correlations between maximum TNF-α concentrations and systemic vascular resistance (p < .01), cardiac index (p < .02), Lung Injury Score (p < .02), prothrombin time (p < .02), and activated partial thromboplastin time (p < .05). Conclusions: Hyperthermic isolated limb perfusion with recombinant TNF-α leads to high systemic concentrations of TNF-α, probably due to leakage of recombinant TNF-α from the perfusion circuit, mainly through collateral blood flow. A sepsis-like syndrome is seen in all patients. Despite high concentrations of systemic TNF-α, this sepsis syndrome is short-lived and recovery is rapid and complete in most patients

Changes in laboratory values and their relationship with time after rupture of an abdominal aortic aneurysm

Many laboratory values are abnormal after surgery for a ruptured abdominal aortic aneurysm (RAAA). However, these changes have not been comprehensively evaluated. We analyzed the changes in routine laboratory values and how these changes related to outcome in a consecutive series of RAAA patients. All patients who underwent surgery for an RAAA between January 1990 and June 2003 at our hospital were included in this study. We analyzed laboratory data acquired during the first week for all patients and at discharge for survivors. We categorized 29 different measurements into six categories based on the related pathological process, including hematology and coagulation, metabolism, systemic inflammation, renal function, liver function, and electrolytes. A total of 290 patients underwent RAAA surgery, with a hospital mortality of 34%. Hemorrhage was the most common cause of early death, whereas multiple-organ failure (MOF) was the most common cause of death several days after surgery. Most laboratory values deviated from normal at multiple time points and they differed significantly between survivors and nonsurvivors. Both survivors and nonsurvivors of RAAA surgery displayed characteristic time-dependent laboratory abnormalities. Awareness of these responses may help us predict patients prone to complications

Altered circadian rhythmicity in patients in the ICU

Patients in the ICU are thought to have abnormal circadian rhythms, but quantitative data are lacking. To investigate circadian rhythms in the ICU, we studied core body temperatures over a 48-h period in 21 patients (59 ± 11 years of age; eight men and 13 women). The circadian phase position for 17 of the 21 patients fell outside the published range associated with morningness/eveningness, which determines the normative range for variability among healthy normal subjects. In 10 patients, the circadian phase position fell earlier than the normative range; in seven patients, the circadian phase position fell later than the normative range. The mean ± SD of circadian displacement in either direction (advance or delay) was 4.44 ± 3.54 h. There was no significant day-to-day variation of the 24-h temperature profile within each patient. Stepwise linear regression was performed to determine if age, sex, APACHE (Acute Physiology and Chronic Health Evaluation) III score, or day in the ICU could predict the patient-specific magnitude of circadian displacement. The APACHE III score was found to be significantly predictive of circadian displacement. The findings indicate that circadian rhythms are present but altered in patients in the ICU, with the degree of circadian abnormality correlating with severity of illness