Effect of anaesthesia type on postoperative mortality and morbidities: a matched analysis of the NSQIP database.

BACKGROUND: The anaesthetic technique may influence clinical outcomes, but inherent confounding and small effect sizes makes this challenging to study. We hypothesized that regional anaesthesia (RA) is associated with higher survival and fewer postoperative organ dysfunctions when compared with general anaesthesia (GA). METHODS: We matched surgical procedures and type of anaesthesia using the US National Surgical Quality Improvement database, in which 264,421 received GA and 64,119 received RA. Procedures were matched according to Current Procedural Terminology (CPT) and ASA physical status classification. Our primary outcome was 30-day postoperative mortality and secondary outcomes were hospital length of stay, and postoperative organ system dysfunction. After matching, multiple regression analysis was used to examine associations between anaesthetic type and outcomes, adjusting for covariates. RESULTS: After matching and adjusting for covariates, type of anaesthesia did not significantly impact 30-day mortality. RA was significantly associated with increased likelihood of early discharge (HR 1.09; P< 0.001), 47% lower odds of intraoperative complications, and 24% lower odds of respiratory complications. RA was also associated with 16% lower odds of developing deep vein thrombosis and 15% lower odds of developing any one postoperative complication (OR 0.85; P < 0.001). There was no evidence of an effect of anaesthesia technique on postoperative MI, stroke, renal complications, pulmonary embolism or peripheral nerve injury. CONCLUSIONS: After adjusting for clinical and patient characteristic confounders, RA was associated with significantly lower odds of several postoperative complications, decreased hospital length of stay, but not mortality when compared with GA.

Feasibility and safety of early combined cognitive and physical therapy for critically ill medical and surgical patients: the Activity and Cognitive Therapy in ICU (ACT-ICU) trial.

PURPOSE: Cognitive impairment after critical illness is common and debilitating. We developed a cognitive therapy program for critically ill patients and assessed the feasibility and safety of administering combined cognitive and physical therapy early during a critical illness. METHODS: We randomized 87 medical and surgical ICU patients with respiratory failure and/or shock in a 1:1:2 manner to three groups: usual care, early once-daily physical therapy, or early once-daily physical therapy plus a novel, progressive, twice-daily cognitive therapy protocol. Cognitive therapy included orientation, memory, attention, and problem-solving exercises, and other activities. We assessed feasibility outcomes of the early cognitive plus physical therapy intervention. At 3 months, we also assessed cognitive, functional, and health-related quality of life outcomes. Data are presented as median (interquartile range) or frequency (%). RESULTS: Early cognitive therapy was a delivered to 41/43 (95%) of cognitive plus physical therapy patients on 100% (92-100%) of study days beginning 1.0 (1.0-1.0) day following enrollment. Physical therapy was received by 17/22 (77%) of usual care patients, by 21/22 (95%) of physical therapy only patients, and 42/43 (98%) of cognitive plus physical therapy patients on 17% (10-26%), 67% (46-87%), and 75% (59-88%) of study days, respectively. Cognitive, functional, and health-related quality of life outcomes did not differ between groups at 3-month follow-up. CONCLUSIONS: This pilot study demonstrates that early rehabilitation can be extended beyond physical therapy to include cognitive therapy. Future work to determine optimal patient selection, intensity of treatment, and benefits of cognitive therapy in the critically ill is needed.

Long-term cognitive impairment after critical illness.

BACKGROUND: Survivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized. METHODS: We enrolled adults with respiratory failure or shock in the medical or surgical intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed global cognition and executive function 3 and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status (population age-adjusted mean [±SD] score, 100±15, with lower values indicating worse global cognition) and the Trail Making Test, Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive function). Associations of the duration of delirium and the use of sedative or analgesic agents with the outcomes were assessed with the use of linear regression, with adjustment for potential confounders. RESULTS: Of the 821 patients enrolled, 6% had cognitive impairment at baseline, and delirium developed in 74% during the hospital stay. At 3 months, 40% of the patients had global cognition scores that were 1.5 SD below the population means (similar to scores for patients with moderate traumatic brain injury), and 26% had scores 2 SD below the population means (similar to scores for patients with mild Alzheimer's disease). Deficits occurred in both older and younger patients and persisted, with 34% and 24% of all patients with assessments at 12 months that were similar to scores for patients with moderate traumatic brain injury and scores for patients with mild Alzheimer's disease, respectively. A longer duration of delirium was independently associated with worse global cognition at 3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months. CONCLUSIONS: Patients in medical and surgical ICUs are at high risk for long-term cognitive impairment. A longer duration of delirium in the hospital was associated with worse global cognition and executive function scores at 3 and 12 months. (Funded by the National Institutes of Health and others; BRAIN-ICU ClinicalTrials.gov number, NCT00392795.).

Understanding terminology of delirium and long-term cognitive impairment in critically ill patients.

Delirium, an acute brain dysfunction, frequently affects intensive care unit (ICU) patients during the course of a critical illness. Besides the acute morbidities, ICU survivors often experience long-term sequelae in the form of cognitive impairment (LTCI-CI). Though delirium and LTCI-CI are associated with adverse outcomes, little is known on the terminology used to define these acute and chronic co-morbidities. The use of a correct terminology is a key factor to spread the knowledge on clinical conditions. Therefore, we first review the epidemiology, definition of delirium and its related terminology. Second, we report on the epidemiology of LTCI-CI and compare its definition to other forms of cognitive impairments. In particular, we define mild cognitive impairment, dementia and finally postoperative cognitive dysfunction. Future research is needed to interpret the trajectories of LTCI-CI, to differentiate it from neurodegenerative diseases and to provide a formal disease classification.

Sedation in the intensive care unit.

Analgesics and sedatives are commonly prescribed in the ICU environment for patient comfort, however, recent studies have shown that these medications can themselves lead to adverse patient outcomes. Interventions that facilitate a total dose reduction in analgesic and sedative medications e.g. the use of nurse controlled protocol guided sedation, the combination of spontaneous awakening and breathing trials, and the use of short acting medications, are associated with improved outcomes such as decreased time of mechanical ventilation and ICU length of stay. This purpose of this review is to provide an overview of the pharmacology of commonly prescribed analgesics and sedatives, and to discuss the evidence regarding best prescribing practices of these medications, to facilitate early liberation from mechanical ventilation and to promote animation in critically ill patients.

Insulin-like growth factor-1 and delirium in critically ill mechanically ventilated patients: a preliminary investigation.

BACKGROUND: Delirium occurs frequently in the intensive care unit (ICU), but its pathophysiology is still unclear. Low levels of insulin-like growth factor 1 (IGF-1), a hormone with neuroprotective properties, have been associated with delirium in some non-ICU studies, but this relationship has not been examined in the ICU. We sought to test the hypothesis that low IGF-1 concentrations are associated with delirium during critical illness. METHODS: Mechanically ventilated medical ICU patients were prospectively enrolled, and blood was collected after enrollment for measurement of IGF-1 using radioimmunometric assay. Delirium and coma were identified daily using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale, respectively. The association between IGF-1 and delirium was evaluated with logistic regression. In addition, the association between IGF-1 and duration of normal mental state, measured as days alive without delirium or coma, was assessed using multiple linear regression. RESULTS: Among 110 patients, the median age was 65 years (IQR, 52-75) and APACHE II was 27 (IQR, 22 -32). IGF-1 levels were not a risk factor for delirium on the day after IGF-1 measurement (p = 0.97), at which time 65% of the assessable patients were delirious. No significant association was found between IGF-1 levels and duration of normal mental state (p = 0.23). CONCLUSIONS: This pilot study, the first to investigate IGF-1 and delirium in critically ill patients, found no association between IGF-1 and delirium. Future studies including serial measurements of IGF-1 and IGF-1 binding proteins are needed to determine whether this hormone has a role in delirium during critical illness.

Plasma tryptophan and tyrosine levels are independent risk factors for delirium in critically ill patients.

AIM: The pathophysiology of delirium remains elusive though neurotransmitters and their precursor large neutral amino acids (LNAAs) may play a role. This pilot study investigated whether alterations of tryptophan (Trp), phenylalanine (Phe), and tyrosine (Tyr) plasma levels were associated with a higher risk of transitioning to delirium in critically ill patients. METHODS: Plasma LNAA concentrations were determined on days 1 and 3 in mechanically ventilated (MV) patients from the MENDS randomized controlled trial (dexmedetomidine vs. lorazepam sedation). Three independent variables were calculated by dividing plasma concentrations of Trp, Phe, and Tyr by the sum of all other LNAA concentrations. Delirium was assessed daily using the confusion assessment method for the intensive care unit (CAM-ICU). Markov regression models were used to analyze independent associations between plasma LNAA ratios and transition to delirium after adjusting for covariates. RESULTS: The 97 patients included in the analysis had a high severity of illness (median APACHE II, 28; IQR, 24-32). After adjusting for confounders, only high or very low tryptophan/LNAA ratios (p = 0.0003), and tyrosine/LNAA ratios (p = 0.02) were associated with increased risk of transitioning to delirium, while phenylalanine levels were not (p = 0.27). Older age, higher APACHE II scores and increasing fentanyl exposure were also associated with higher probabilities of transitioning to delirium. CONCLUSIONS: In this pilot study, plasma tryptophan/LNAA and tyrosine/LNAA ratios were associated with transition to delirium in MV patients, suggesting that alterations of amino acids may be important in the pathogenesis of ICU delirium. Future studies evaluating the role of amino acid precursors of neurotransmitters are warranted in critically ill patients.

FLT3 ligand induces the generation of functionally active dendritic cells in mice.

FLT3 ligand (FL) is a recently described hematopoietic growth factor that stimulates the proliferation and differentiation of hematopoietic progenitors. We have investigated the effect of FL on murine hematopoiesis and dendritic cell (DC) generation and accumulation in lymphoid tissues and liver in vivo and in vitro evaluating the morphologic, phenotypic, and functional characteristics of these DC. We have observed extramedullary hematopoiesis in the mouse spleen with all lineages of hematopoietic cells represented after the administration of FL. Injection of FL results in a time-dependent and reversible accumulation of DC in the spleen, bone marrow, lymph nodes, and liver. Both flow cytometry and immunohistochemistry revealed a significant accumulation of DC in these tissues. Results of mixed leukocyte reaction suggested that these cells, isolated from murine bone marrow or spleen, were active as antigen presenting cells. Furthermore, cultivation of splenic and marrow cells with GM-CSF and IL-4 gave rise to large numbers of functionally active mature DC. Thus, the results of this study suggest that FL is a promising growth factor that stimulates the generation of large number of DC and may be a useful cytokine for the immunotherapy of cancer.