Haloperidol prophylaxis for preventing aggravation of postoperative delirium in elderly patients: a randomized, open-label prospective trial.

PURPOSES: The aim of this study was to evaluate the safety and efficacy of the early administration haloperidol in preventing the aggravation of postoperative delirium in elderly patients. METHODS: A total of 201 patients (age ≥75 years) who underwent elective surgery were enrolled. The patients were divided into two groups: the intervention group (n = 101) received prophylactic haloperidol (5 mg); the control group (n = 100) did not. Haloperidol was administered daily during postoperative days 0-5 to the patients who presented with NEECHAM scores of 20-24 when measured at 18:00. The primary endpoint was the incidence of severe postoperative delirium. RESULTS: The incidence of severe postoperative delirium in all patients was 25.1%. The incidence of severe postoperative delirium in the intervention group (18.2%) was significantly lower than that in the control group (32.0%) (p = 0.02). The difference between the two groups was larger when the analysis was limited to the 70 patients who had NEECHAM scores of 20-24 for at least one day during postoperative days 0-5. No adverse effects of the haloperidol were observed. CONCLUSION: The prophylactic administration of haloperidol at the early stage of delirium significantly reduced the incidence of severe postoperative delirium in elderly patients. Clinical Trial Registration UMIN000007204.

Risk Factors for Postoperative Delirium in Abdominal Surgery: A Proposal of a Postoperative Delirium Risk Score in Abdominal Surgery.

BACKGROUND/AIMS: Despite the presence of several diagnosis scales for delirium, no prediction scale that is specific for postoperative delirium after abdominal surgery is available. We sought to create a novel delirium prediction system that is specific for abdominal surgery. METHODS: This study included 213 consecutive patients who required management in the surgical ICU following abdominal surgery. The Neelon and Champagne (NEECHAM) Confusion score was monitored throughout the postoperative course and patients with low NEECHAM score (≤26) were diagnosed as having delirium. RESULTS: Seventy-three patients (34%) were categorized in the delirium group. Multivariate analyses indicated that an age >70 years, hypertension, those undergoing hepatopancreatobiliary or upper gastrointestinal surgeries, a serum albumin level <2.5 g/dl on postoperative day (POD) 3 or 5 and a ≥6 mEq/l gap in the serum sodium level between the preoperative value and that on POD 3 were independently associated with a low NEECHAM score (≤26). When the presence of each risk was counted as 1 point, 21 patients had ≥4 points and 15 of them (71%) had low NEECHAM score. CONCLUSION: The scoring system combining multiple risk factors may be useful for predicting patients with an elevated risk for postoperative delirium after abdominal surgery.

Haloperidol prophylaxis does not prevent postoperative delirium in elderly patients: a randomized, open-label prospective trial.

PURPOSE: Postoperative delirium is the most common postoperative complication in the elderly. The purpose of this study was to evaluate the safety and effectiveness of the preventive administration of low-dose haloperidol on the development of postoperative delirium after abdominal or orthopedic surgery in elderly patients. SUBJECTS: A total of 119 patients aged 75 years or older who underwent elective surgery for digestive or orthopedic disease were included in this study. METHODS: Patients were divided into those who did (intervention group, n = 59) and did not (control group, n = 60) receive 2.5 mg of haloperidol at 18:00 daily for 3 days after surgery; a randomized, open-label prospective study was performed on these groups. The primary endpoint was the incidence of postoperative delirium during the first 7 days after the operation. RESULTS: The incidence of postoperative delirium in all patients was 37.8%. No side effects involving haloperidol were noted; however, the incidences of postoperative delirium were 42.4 and 33.3% in the intervention and control groups, respectively, which were not significantly different (p = 0.309). No significant effect of the treatment was observed on the severity or persistence of postoperative delirium. CONCLUSIONS: The preventive administration of low-dose haloperidol did not induce any adverse events, but also did not significantly decrease the incidence or severity of postoperative delirium or shorten its persistence.

Postoperative function following radical surgery in gastric and colorectal cancer patients over 80 years of age--an objection to "ageism".

PURPOSE: With rapid growth in the elderly population, the number of elderly cancer patients who should be offered life-prolonging radical surgery has been increasing. The aim of this report is to demonstrate the outcome of elective radical surgery for gastric or colorectal cancer patients 80 years of age or older, including the natural course of recovery of functional independence, in order to avoid the negative attitude held toward surgery that is due only to patients' high chronological age. METHODS: Physical condition, ADL, and QOL of 108 patients 80 years of age or older with gastric or colorectal cancer were evaluated preoperatively and at the 1st, 3rd, and 6th postoperative months. RESULTS: There were no operative deaths, and the morbidity rate was 27.9%. Only 6% of the patients showed a decrease in ADL at the 6th postoperative month. This decrease typically occurred following discharge from the hospital. Patient QOL showed recovery to an extent equal to or better than average preoperative scores. CONCLUSIONS: Of the patients who underwent elective surgery for gastric or colorectal cancer, only a few showed a protracted decline in ADL, and most exhibited better QOL after surgery. Surgical treatment should therefore be considered, whenever needed, for elderly patients 80 years of age or older with gastric or colorectal cancer.

Assessment of the risk of postoperative delirium in elderly patients using E-PASS and the NEECHAM Confusion Scale.

BACKGROUND: The incidences of surgery-field disorders such as femur neck fracture and colorectal cancer in elderly persons have increased with the rapid aging of society. In such patients, postoperative delirium is also frequent. Patients should be generally assessed from the aspect of both physical and mental conditions in order to predict a high-delirium risk group. If so, delirium may be prevented more efficiently. In this study, we investigated whether the early detection of postoperative delirium in elderly patients is possible using a simple, useful behavior-assessing scale, the NEECHAM Confusion Scale, and a method for comprehensively evaluating elderly persons' stress related to surgery, E-PASS. METHODS: The subjects were 160 patients aged more than 75 years who underwent surgery. Among them, three patients had vascular surgery-field disorders, 67 had orthopedic-field disorders, and 90 had digestive surgery-field disorders. To comprehensively evaluate surgery-related stress, E-PASS was employed. In addition, we assessed recognition, activities of daily living (ADL), and the quality of life (QOL). For delirium diagnosis and severity assessment, we used the NEECHAM Confusion Scale. The cut-off value of the NEECHAM score was established as 20 points, and patients showing values less than this after surgery were regarded as having postoperative delirium. Evaluation was performed until 10 days after surgery. RESULTS: Postoperative delirium was noted in 54.7% of the subjects. There was a decrease in the NEECHAM score between the first and fourth postoperative days, but it gradually increased thereafter. Both uni- and multivariate analyses showed that postoperative delirium was associated with an advanced age (more than 80 years), low preoperative NEECHAM and MMSE scores, the preoperative QOL, and E-PASS. In groups showing an MMSE score of less than 25 or a preoperative NEECHAM score of less than 27, the incidence of postoperative delirium was 76%. CONCLUSION: The results suggest that E-PASS and the NEECHAM score facilitate assessment of the risk of postoperative delirium in elderly patients, contributing to early prevention/treatment.

Activities of daily living and quality of life of elderly patients after elective surgery for gastric and colorectal cancers.

OBJECTIVE: To establish reliable standards for surgical application to elderly patients 75 years old or older with gastric or colorectal cancer with special reference to the postoperative recovery of activities of daily living (ADL) and quality of life (QOL). SUMMARY BACKGROUND DATA: ADL and QOL are important outcomes of surgery for the elderly. However, there has been only limited evidence on the natural course of recovery of functional independence. METHODS: Two hundred twenty-three patients 75 years old or older with gastric or colorectal cancer were prospectively examined. Physical conditions, ADL, and QOL were evaluated preoperatively and at the first, third, and sixth postoperative month. RESULTS: The mortality and morbidity rates were 0.4% and 28%, respectively. Twenty-four percent of patients showed a decrease in ADL at 1 month postoperatively, but most patients recovered from this transient reduction, with only 3% showing a decline at the sixth postoperative month (6POM). ADL of these patients was likely to decrease after discharge from the hospital. QOL of the patients showed a recovery to an extent equal to or better than their average preoperative scores. CONCLUSIONS: Of the patients 75 years old or older who underwent elective surgery for gastric or colorectal cancer, only a few showed a protracted decline in ADL and most exhibited better QOL after surgery. This indicates that surgical treatment should be considered, whenever needed, for elderly patients 75 years old or older with gastric or colorectal cancer. Estimation of Physical Ability and Surgical Stress is useful for predicting postoperative declines in ADL and protracted disability; this could aid in establishing a directed rehabilitation program for preventing protracted disability in elderly patients.

Anti-high-mobility group box chromosomal protein 1 antibodies improve survival of rats with sepsis.

BACKGROUND: High-mobility group box chromosomal protein 1 (HMGB1) has recently been shown to be an important late mediator of endotoxin shock, intraabdominal sepsis, and acute lung injury, and a promising therapeutic target of severe sepsis. We sought to investigate the effect of antibodies to HMGB1 on severe sepsis in a rat cecal ligation and puncture (CLP) model. METHODS: Adult male Sprague-Dawley rats underwent CLP and then were randomly divided into two groups: treatment with anti-HMGB1 polyclonal antibodies, and non-immune IgG-treated controls. The serum HMGB1 concentrations were measured at ten time points (preoperatively, and postoperatively at 4, 8, 20, 32, and 48 h and at 3, 4, 5, and 6 days). Hematoxylin-eosin staining, elastica-Masson staining, and immunohistochemical staining for HMGB1 were performed on the cecum and the lung to assess pathological changes 24 h after the CLP procedure. RESULTS: Treatment with anti-HMGB1 antibodies significantly increased survival [55% (anti-HMGB1) vs. 9% (controls); P< 0.01]. The serum HMGB1 concentrations at postoperative hours 20 and 32 of the anti-HMGB1 antibody-treated animals were significantly lower than those of the controls (P < 0.05). Treatment with anti-HMGB1 antibodies markedly diminished the pathological changes and the number of HMGB1-positive cells in the cecum and the lung. CONCLUSIONS: The present study demonstrates that anti-HMGB1 antibodies are effective in the treatment of severe sepsis in a rat model, thereby supporting the relevance of HMGB1 eradication therapy for severe sepsis.