Serum anticholinergic activity and postoperative cognitive dysfunction in elderly patients

Background: Cerebral cholinergic transmission plays a key role in cognitive function and anticholinergic drugs are associated with impaired cognitive functions [1]. In the perioperative phase many substances with anticholinergic effects are administered and disturbed cholinergic transmission is a hypothetical cause of postoperative cognitive dysfunction (POCD). Serum anticholinergic activity (SAA; pmol/ml) may be measured as a summary marker of anticholinergic activity in an individual patient's blood. We hypothesised that an increase in SAA from preoperatively to one week postoperatively is associated with POCD in elderly patients. Methods: Thirty-two patients aged >65 yrs undergoing elective major surgery under standardized general anaesthesia (thiopental, sevoflurane, fentanyl) were investigated. Cognitive functions were measured preoperatively and 7 days postoperatively using the extended version of the Consortium to Establish a Registry for Alzheimer's Disease - Neuropsychological Assessment Battery. POCD was defined as a postoperative decline >1 z-score in at least 2 cognitive domains. SAA was measured preoperatively and 7 days postoperatively at the time of cognitive testing. Results: 50% of the investigated patients developed POCD. There were no statistically significant differences between patients with and without POCD regarding age, education, baseline cognitive function, duration of anaesthesia, SAA preoperatively (median (range) 1.0 (0.3 to 5.0) vs 1.5 (0.4 to 5.0), SAA 7 days postoperatively (median (range) 1.3 (0.1 to 7.0) vs 1.4 (0.6 to 5.5) or changes in SAA (median (range) 0.1 (-1.6 to 2.2) vs 0.2 (-1.4 to 2.8). The variability of SAA in individual patients was considerable and marked changes in SAA between the two examinations were observed in some patients. However, there was no significant relationship between changes in SAA and changes in cognitive function. Conclusion: In this preliminary analysis of a small group of patients, changes in SAA in the perioperative phase were highly variable. SAA was not associated with POCD suggesting that POCD is not simply caused by anticholinergic medications administered in the perioperative phase. A further analysis of a larger group of patients is in progress.

Giant warts in a kidney transplant patient: regression with sirolimus.

Purpose: Recent reports have suggested that intraabdominal postoperative infection is associated with higher rates of overall and local recurrence and cancer-specific mortality. However, the mechanisms responsible for this association are unknown. We hypothesized that the greater inflammatory response in patients with postoperative intraabdominal infection is associated to an increase in local and systemic angiogenesis. Methods: We designed a prospective cohorts study with matched controls. Patients with postoperative intra-abdominal infection (abscess and/or anastomotic leakage) (group 1; n=17) after elective colorectal cancer resection operated on for cure were compared to patients with an uncomplicated postoperative course (group 2; n=17). IL-6 and VEGF levels were determined by ELISA in serum and peritoneal fluid at baseline, 48 hours and postoperative day 4 or at the time the peritoneal infection occurred. Results: No differences were observed in age, gender, preoperative CEA, tumor stage and location and type of procedure performed. Although there were no differences in serum IL-6 levels at 48 hours, this pro-inflammatory cytokine was higher in group 1 on postoperative day 4 (group 1: 21533 + 27900 vs. group 2: 1130 + 3563 pg/ml; p < 0.001). Serum VEGF levels were higher in group 1 on postoperative day 4 (group 1: 1212 + 1025 vs. group 2: 408 + 407 pg/ml; p < 0.01). Peritoneal fluid VEGF levels were also higher in group 1 at 48 hours (group 1: 4857 + 4384 vs. group 2: 630 + 461 pg/ml; p < 0.001) and postoperative day 4 (group 1: 32807 + 98486 vs. group 2: 1002 + 1229 pg/ml; p < 0.001). A positive correlation between serum IL-6 and VEGF serum levels was observed on postoperative day 4 (r=0.7; p<0.01). Conclusions: These results suggest that not only the inflammatory response but also the angiogenic pathways are stimulated in patients with intra-abdominal infection after surgery for colorectal cancer. The implications of this finding on long-term follow-up need to be evaluated.

Neurolysis using a carbohydrate polymer gel for the treatment of postoperative neuropathic pain.

Perineural and intraneural fibrosis is thought to be the main cause of failure of the many surgical treatments of neuropathic pain. We have used Adcon-T/N carbohydrate polymer gel for prevention of perineural fibrosis in several parts of the body. In this retrospective study, 54 patients who presented with postoperative neuropathic pain had microsurgical epineural neurolysis and relocation of a terminal neuroma. In 19 of them, the carbohydrate gel was applied at the same time. The mean follow-up was four years and the nerve distribution varied. Postoperative improvement in pain scores (visual analogue scale (VAS) and neuropathic pain scale inventory (NPSI)), sensitivity, overall improvement and satisfaction were equivalent in the two groups, with pain relief in about 80% of the patients. There was no significant beneficial effect in the carbohydrate gel group. Patients treated with this device had a higher infection rate (21 compared with 0, p = 0.01) and delayed wound healing (31.6 compared with 11.8, p = 0.2). We conclude that good long-term pain relief is obtained postoperatively independently of the addition of carbohydrate gel. There was a slight but not significant trend towards profound pain relief with the gel.

Prognostic value of postoperative carcinoembryonic antigen concentration and extent of invasion of resection margins after hepatic resection for colorectal metastases.

OBJECTIVE: To evaluate the prognostic value of postoperative concentration of carcinoembryonic antigen (CEA) and extent of surgical margins after resection of liver metastases from colorectal cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Switzerland. SUBJECTS: 49 patients with hepatic metastases after primary colorectal cancer. INTERVENTIONS: Resection of hepatic metastases MAIN OUTCOME MEASURES: Assessment of prognostic value of variables by univariate and multivariate analysis. RESULTS: Median survival was 24 months (range 5-86 months). Resection margins were clear (> 1-cm) in 10, close (< 1-cm) in 25 and invaded in 9 patients. On univariate analysis, a postoperative concentration of CEA of <4ng/ml was correlated with prolonged survival (p < 0.001), but the width of the resection margin was not of prognostic importance. There was no correlation between width of resection margins and postoperative concentration of CEA (p = 0.5). On multivariate analysis, postoperative concentrations of CEA of 4 ng/ml or more were associated with increased risk of death (relative risk 7.3; 95% confidence interval (CI) 2.8-18.7, p < 0.001). CONCLUSION: Postoperative CEA offers better prognostic discrimination than the width of resection margins after resection of liver metastases from colorectal tumours. Some patients with invaded resection margins did survive for 3 years, but no patient did whose CEA concentration was 4 ng/ml or more. The definition of a potentially curative hepatic resection should include a postoperative CEA concentration of <4 ng/ml (within the reference range).

Fatal myocardial infarction after lung resection in a patient with prophylactic preoperative coronary stenting.

In this report we present the case of a 77-yr-old man who underwent resection of the upper lobe of the left lung for a carcinoma, six weeks after percutaneous transluminal coronary angioplasty (PTCA) with stenting of the left anterior descending (LAD) and circumflex coronary arteries. Antiplatelet therapy with clopidogrel was interrupted two weeks before surgery to allow for epidural catheter placement and to minimize haemorrhage. The surgical procedure was uneventful. In the immediate postoperative period, however, the patient suffered severe myocardial ischaemia. Emergency coronary angiography showed complete thrombotic occlusion of the LAD stent. In spite of successful recanalization, reinfarction occurred and the patient died in cardiogenic shock. Prophylactic preoperative coronary stenting may put the patient at risk of stent thrombosis if surgery cannot be postponed for three months. In such cases, other strategies such as perioperative beta-blockade for preoperative cardiac management should be considered.

Liver Transplantation for Neuroendocrine Tumors in Europe-Results and Trends in Patient Selection: A 213-Case European Liver Transplant Registry Study.

OBJECTIVE:: The purpose of this study was to assess outcomes and indications in a large cohort of patients who underwent liver transplantation (LT) for liver metastases (LM) from neuroendocrine tumors (NET) over a 27-year period. BACKGROUND:: LT for NET remains controversial due to the absence of clear selection criteria and the scarcity and heterogeneity of reported cases. METHODS:: This retrospective multicentric study included 213 patients who underwent LT for NET performed in 35 centers in 11 European countries between 1982 and 2009. One hundred seven patients underwent transplantation before 2000 and 106 after 2000. Mean age at the time of LT was 46 years. Half of the patients presented hormone secretion and 55% had hepatomegaly. Before LT, 83% of patients had undergone surgical treatment of the primary tumor and/or LM and 76% had received chemotherapy. The median interval between diagnosis of LM and LT was 25 months (range, 1-149 months). In addition to LT, 24 patients underwent major resection procedures and 30 patients underwent minor resection procedures. RESULTS:: Three-month postoperative mortality was 10%. At 5 years after LT, overall survival (OS) was 52% and disease-free survival was 30%. At 5 years from diagnosis of LM, OS was 73%. Multivariate analysis identified 3 predictors of poor outcome, that is, major resection in addition to LT, poor tumor differentiation, and hepatomegaly. Since 2000, 5-year OS has increased to 59% in relation with fewer patients presenting poor prognostic factors. Multivariate analysis of the 106 cases treated since 2000 identified the following predictors of poor outcome: hepatomegaly, age more than 45 years, and any amount of resection concurrent with LT. CONCLUSIONS:: LT is an effective treatment of unresectable LM from NET. Patient selection based on the aforementioned predictors can achieve a 5-year OS between 60% and 80%. However, use of overly restrictive criteria may deny LT to some patients who could benefit. Optimal timing for LT in patients with stable versus progressive disease remains unclear.

Comparison of multislice computerized tomography angiography and digital subtraction angiography in the postoperative evaluation of patients with clipped aneurysms.

OBJECT: In this study the accuracy of multislice computerized tomography (MSCT) angiography in the postoperative examination of clip-occluded intracranial aneurysms was compared with that of intraarterial digital subtraction (DS) angiography METHODS: Forty-nine consecutive patients with 60 clipped aneurysms (41 of which had ruptured) were studied with the aid of postoperative MSCT and DS angiography. Both types of radiological studies were reviewed independently by two observers to assess the quality of the images, the artifacts left by the clips, the completeness of aneurysm occlusion, the patency of the parent vessel, and the duration and cost of the examination. The quality of MSCT angiography was good in 42 patients (86%). Poor-quality MSCT angiograms (14%) were a result of the late acquisition of images in three patients and the presence of clip or motion artifacts in four. Occlusion of the aneurysm on good-quality MSCT angiograms was confirmed in all but two patients in whom a small (2-mm) remnant was confirmed on DS angiograms. In one patient, occlusion of a parent vessel was seen on DS angiograms but missed on MSCT angiograms. The sensitivity and specificity for detecting neck remnants on MSCT angiography were both 100%, and the sensitivity and specificity for evaluating vessel patency were 80 and 100%, respectively (95% confidence interval 29.2-100%). Interobserver agreements were 0.765 and 0.86, respectively. The mean duration of the examination was 13 minutes for MSCT angiography and 75 minutes for DS angiography (p < 0.05). Multislice CT angiography was highly cost effective (p < 0.01). CONCLUSIONS: Current-generation MSCT angiography is an accurate noninvasive tool used for assessment of clipped aneurysms in the anterior circulation. Its high sensitivity and low cost warrant its use for postoperative routine control examinations following clip placement on an aneurysm. Digital subtraction angiography must be performed if the interpretation of MSCT angiograms is doubtful or if the aneurysm is located in the posterior circulation.

Effects of L-carnitine supplemented total parenteral nutrition on lipid and energy metabolism in postoperative stress.

During episodes of trauma carnitine-free total parenteral nutrition (TPN) may result in a reduction of the total body carnitine pool, leading to a diminished rate of fat oxidation. Sixteen patients undergoing esophagectomy were divided randomly in two equal isonitrogenous groups (0.2 g/kg.day). Both received TPN (35 kcal/kg.day; equally provided as long-chain triglycerides and glucose) over 11 days without (group A) and with (group B) L-carnitine supplementation (12 mg/kg.day = 75 mumol/kg.day). Compared with healthy controls, the total body carnitine pool prior to the operation was significantly reduced in both groups, suggesting a state of semistarvation and muscle wasting. In group A the plasma levels of total carnitine and its subfractions (free carnitine, short- and long-chain acylcarnitine) remained stable during the study whereas in group B the total plasma carnitine concentration rose mainly due to an increase in free carnitine. In group A the cumulative urinary carnitine losses were 11.5 +/- 2.6 mmol (= 15.5 +/- 3.1% of the estimated total body carnitine pool). In group B 3.1 +/- 1.9 mmol (= 11.1 +/- 7.6%) of the infused carnitine was retained in the immediate postoperative phase until day 6, but this amount was completely lost at completion of the study period. No significant differences in the respiratory quotient or in the plasma levels of triglycerides, free fatty acids, and ketone bodies were observed, between or within the groups, before the operation and after 11 days of treatment. It is concluded that the usefulness of carnitine supplementation during postoperative TPN was not apparent in the present patient material.

Is the effect of inguinal field block with 0.5 % bupivacaine on postoperative pain after hernia repair enhanced by addition of ketorolac or S(+) ketamine ?

Résumé Malgré l'apparition de nouvelles techniques chirurgicales dites « sans tension », l'antalgie post-opératoire après cure de hernie inguinale reste un défi pour les anesthésiologistes. Récemment on a suggéré que l'addition de ketamine ou d'un anti-inflammatoire non-stéroïdien (AINS) à un anesthésique local pourrait améliorer et prolonger l'analgésie postopératoire. Le but de cette étude, à laquelle ont participé 36 patients ASA I-II, était d'évaluer si la coadministration de S(+) ketamine ou de ketorolac renforcerait les effets analgésiques de la bupivacaïne après cure ambulatoire de hernie inguinale sous anesthésie générale. L'analgésie a consisté en une infiltration de la plaie associé à un bloc inguinal avec soit 30 ml de bupivacaïne 0,5 % (n=12), soit 27 ml de bupivacaïne 0,5 % + 3 ml de S(+) ketamine (75 mg) (n=12), soit 28 ml de bupivacaïne 0,5 % + 2 ml de ketorolac (60 mg) (n=12). La prise orale d'antalgique en phase postopératoire était standardisée. L'intensité des douleurs a été évaluée au moyen d'une échelle visuelle analogique (EVA), d'un score verbal d'estimation et par algométrie de pression respectivement 2, 4, 6, 24 et 48 heures après l'intervention. Les trois groupes de patients ont présenté le score de douleur évalué par EVA le plus élevé à 24 heures, score significativement différent de ceux mesurés à 6 et 48 heures (P <0.05). A part une sensation de douleurs significativement moindre (score verbal d'estimation) dans le groupe ketorolac à 24 et 48 heures et seulement à 48 heures dans le groupe ketamine, il n'y avait aucune autre différence entre les groupes pour la durée de l'étude (48 heures) en ce qui concerne les scores de douleur, les seuils de douleur à la pression ou la prise postopératoire d'antalgiques « de secours ». En conclusion, l'addition de S(+) ketamine ou de ketorolac, n'améliore que marginalement l'effet analgésique de la bupivacaïne. Ceci peut-être mis en relation avec la technique de cure de hernie « sans tension » induisant un bas niveau de douleur postopératoire. Abstract Objective: The aim of the study was to assess whether coadministration of S(±) ketamine or ketorolac would enhance or prolong local analgesic effect of bupivacaine after inguinal hernia repair. Design: Prospective double-blind randomized study evaluating pain intensity after surgery under general anesthesia. Setting: Outpatient facilities of the University Hospital of Lausanne. Patient: Thirty-six ASA I-II outpatients scheduled for elective day-case inguinal herniorraphy. Intervention: Analgesia strategy consisted of a wound infiltration and an inguinal field block either with 30 mL bupivacairie (0.5%) or with the same volume of a mixture of 27 mL bupivacaine (0.5%) + 3 mL S(+) ketamine (75 mg) or a 28 mL bupivacaine (0.5%) + 2 ML ketorolac (60 mg). Postoperative analgesic regimen was standardized. Outcome Measures: Pain intensity was assessed with a Visual Analog Seale, a verbal rating score, and by pressure algometry 2, 4, 6, 24, and 48 hours after surgery. Results: The 3 groups of patients experienced the highest Visual Analog Scale pain score at 24 hours, which was different from those at 6 and 48 hours (P < 0.05). Apart from a significantly lower pain sensation (verbal rating score) in the ketorolac group at 24 and 48 hours and only at 48 hours with ketamine, there were no other differences in pain scores, pain pressure thresholds, or rescue analgesic consumption between groups throughout the 48-hour study period. Conclusion: The addition of S (+)-ketamine or ketorolac only minimally improves the analgesic effect of bupivacaine. This may be related to the tension-free hernia repair technique associated with low postoperative pain.

Correction of pectus excavatum combined with open heart surgery in a patient with Marfan's syndrome.

We report a patient with Marfan's syndrome and pectus excavatum who underwent open heart surgery with simultaneous correction of the sternal malformation. Permanent internal stabilization, achieved by bilateral overlapping of the bevelled ends of the lowest ribs and reinforced with sternal closure wires offered a maintained postoperative chest wall stability, avoided the potential postoperative complications of cardiac compression, and improved the aesthetic appearance of the anterior chest wall. The increased risk of bleeding due to extensive dissection was minimized by postponing the repair of pectus excavatum to when protamin is administered after termination of cardiopulmonary bypass.

Postoperative subconjunctival mitomycin-C injection after non-penetrating glaucoma surgery.

PURPOSE: To evaluate subconjunctival mitomycin C (MMC) injection efficacy and safety in patients with failing glaucoma non-penetrating filtering blebs. METHODS: Twenty-eight eyes were consecutively recruited for this study. Only one eye for each patient was randomly selected. All the recruited patients had glaucoma and uncontrolled intraocular pressure after a non-penetrating filtering glaucoma surgery and/or a pathological aspect of the filtering bleb (i.e., vascularized and/or encysted). One or more MMC injections were performed under the conjunctiva closed to the bleb to improve filtration. Local effects and complications of subconjunctival MMC injections were analyzed. RESULTS: Out of the 28 patients, 21 (75%) had MMC also applied intraoperatively. The mean postoperative IOP before MMC injections was 17 +/- 6.6 mmHg. The final IOP after MMC injections was 13.9 +/- 2.9 mmHg after a mean follow-up of 6 months. A total of 67 subconjunctival MMC injections were performed with a mean of 2.9 (ranging from 1 to 5) injections per patient. The only complication found to be possibly related to MMC injections was two cases of corneal Dellen. CONCLUSION: From these preliminary results, subconjunctival MMC injections in selected cases appear to be not only safe but also effective in promoting further the postoperative IOP drop.

Postoperative management of adult central neurosurgical patients: systemic and neuro-monitoring.

Postoperative neurosurgical patients are at risk of developing complications. Systemic and neuro-monitoring are used to identify patients who deteriorate in order to treat the underlying cause and minimize the impact on outcome. Hypotension and hypoxia are likely to be the most frequent insults and can be detected easily with blood pressure monitoring and pulse oximetry. Repeated clinical examination, however, is probably the most important monitor in the postoperative setting. Clinical scores such as the Glasgow Coma Score and the more recently introduced FOUR Score are important tools to standardize the clinical assessment. Intracranial pressure monitoring, cerebral blood flow monitoring, electroencephalography, and brain imaging are often used postoperatively. Despite the numerous publications on this topic only few studies address the impact of postoperative monitoring on outcome. Accordingly, in most patients the decision on which monitors are to be used must be based on the patient's presentation and clinical judgment.

Postoperative delirium. Part 2: detection, prevention and treatment.

To target pharmacological prevention, instruments giving an approximation of an individual patient's risk of developing postoperative delirium are available. In view of the variable clinical presentation, identifying patients in whom prophylaxis has failed (that is, who develop delirium) remains a challenge. Several bedside instruments are available for the routine ward and ICU setting. Several have been shown to have a high specificity and sensitivity when compared with the standard definitions according to DSM-IV-TR and ICD-10. The Confusion Assessment Method (CAM) and a version specifically developed for the intensive care setting (CAM-ICU) have emerged as a standard. However, alternatives allowing grading of the severity of delirium are also available. In many units, the approach to delirium follows a three-step strategy. Initially, non-pharmacological multicomponent strategies are used for primary prevention. As a second step, pharmacological prophylaxis may be added. Perioperative administration of haloperidol has been shown to reduce the severity, but not the incidence, of delirium. Perioperative administration of atypical antipsychotics has been shown to reduce the incidence of delirium in specific groups of patients. In patients with delirium, both symptomatic and causal treatment of delirium need to be considered. So far symptomatic treatment of delirium is primarily based on antipsychotics. Currently, cholinesterase inhibitors cannot be recommended and the data on dexmedetomidine are inconclusive. With the exception of alcohol-withdrawal delirium, there is no role for benzodiazepines in the treatment of delirium. It is unclear whether treating delirium prevents long-term sequelae.

Modelling the effect of minor orthopaedic day surgery on patient mood at the early post-operative period: a prospective population-based cohort study.

OBJECTIVE: The effect of minor orthopaedic day surgery (MiODS) on patient's mood. METHODS: A prospective population-based cohort study of 148 consecutive patients with age above 18 and less than 65, an American Society of Anaesthesiology (ASA) score of 1, and the requirement of general anaesthesia (GA) were included. The Medical Outcomes Study - Short Form 36 (SF-36), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) were used pre- and post-operatively. RESULTS: The mean physical component score of SF-36 before surgery was 45.3 (SD=+/-10.1) and 8 weeks following surgery was 44.9 (SD=+/-11.04) [n=148, p=0.51, 95% CI=(-1.03 to 1.52)]. For the measurement of the changes in mood using BDI, BAI and SF-36, latent construct modelling was employed to increase validity. The covariance between mood pre- and post-operatively (cov=69.44) corresponded to a correlation coefficient, r=0.88 indicating that patients suffering a greater number of mood symptoms before surgery continue to have a greater number of symptoms following surgery. When the latent mood constructs were permitted to have different means the model fitted well with chi(2) (df=1)=0.86 for which p=0.77, thus the null hypothesis that MiODS has no effect on patient mood was rejected. CONCLUSIONS: MiODS affects patient mood which deteriorates at 8 weeks post-operatively regardless of the pre-operative patient mood state. More importantly patients suffering a greater number of mood symptoms before MiODS continue to have a greater number of symptoms following surgery.

Combined islet-lung transplantation in a cystic fibrosis patient.

The prevalence of insulin-dependent diabetes mellitus (IDDM) in cystic fibrosis patients ranges from 2 to 8% and glucose intolerance up to 15%. In recent years, lung transplantation has helped to prolong life expectancy of cystic fibrosis patients and represents 10 to 30% of all indications for lung transplantation. The postoperative need for immunosuppressive therapy using diabetogenic agents has decompensatory effects on glucose regulation and will probably increase the number of insulin-dependent cystic fibrosis patients. We report the case of an insulin-dependent cystic fibrosis patient transplanted with a combined islet-lung allograft. The pre-transplantation C-peptide level was below 0.04 nmol/l and preoperative insulin requirement was some 100 U per day. A sequential bipulmonary lung transplantation was performed and, using the pancreas of the same donor, we isolated and purified the islets of Langerhans by a modified automated method. We obtained 232,200 islets equivalent, which were injected into the liver by portal embolization. The postoperative course was uncomplicated, the insulin requirement decreased to 50% of the preoperative need and the C-peptide value increased to normal values and remained with the normal range during a follow-up period of 15 months. In conclusion, we believe that, besides type I diabetic patients, insulin-dependent cystic fibrosis patients with a negative C-peptide value could also be good candidates for combined islet-lung allotransplantation.