Aarne Feldheiser

Enhanced Recovery After Surgery (ERAS) for gastrointestinal surgery, part 2: consensus statement for anaesthesia practice

The present interdisciplinary consensus review proposes clinical considerations and recommendations for anaesthetic practice in patients undergoing gastrointestinal surgery with an Enhanced Recovery after Surgery (ERAS) programme.

Balanced crystalloid compared with balanced colloid solution using a goal-directed haemodynamic algorithm

BACKGROUND Controversy exists regarding the optimal i.v. fluids for use with a goal-directed haemodynamic algorithm. METHODS In a double-blind pilot study, we randomly assigned 50 patients with primary ovarian cancer undergoing cytoreductive surgery to receive either balanced crystalloid or balanced starch (HES, 130/0.4, 6%) solutions up to the dose limit (50 ml kg(-1)). Fluids were administered to optimize stroke volume measured by oesophageal Doppler within a goal-directed haemodynamic algorithm. RESULTS Baseline subject characteristics were similar in both groups. The balanced HES solution maintained stroke volume (P=0.012) better with administration of less fluid. Subjects in the colloid group reached the dose limits of the study medication less frequently (92% vs 62%, P=0.036) and later (2:26 vs 3:33 h, P=0.006) and also required less transfusion of fresh-frozen plasma units (6.0 vs 3.5 units, P=0.035) compared with the crystalloid group. Intra- and postoperative urine output and perioperative plasma levels of creatinine and neutrophil gelatinase-associated lipocalin as renal injury marker were similar in both groups. No differences in the length of intensive care unit and hospital stay were found. CONCLUSIONS Using a goal-directed haemodynamic algorithm to optimize stroke volume, a balanced HES solution is associated with better haemodynamic stability and reduced need for fresh-frozen plasma. There were no signs of renal impairment by colloid solutions when fluid administration is targeted to optimize cardiac preload.

Enhanced Recovery After Surgery (ERAS) for gastrointestinal surgery, part 1: pathophysiological considerations

The present article has been written to convey concepts of anaesthetic care within the context of an Enhanced Recovery After Surgery (ERAS) programme, thus aligning the practice of anaesthesia with the care delivered by the surgical team before, during and after surgery.

Development and Feasibility Study of an Algorithm for Intraoperative Goal-Directed Haemodynamic Management in Noncardiac Surgery

This study developed an evidence-based, goal-directed haemodynamic management algorithm to standardize intraoperative haemodynamic therapy. A systematic literature search identified three haemodynamic management goals: stroke volume optimization by fluid therapy; maintenance of a target mean arterial pressure by vasopressor therapy; maintenance of a target cardiac index ≥ 2.5 l/min per m2 by inotropic therapy. The algorithm was adapted to international standards and consensus was reached through a modified Delphi method at international meetings. Implementation of the algorithm into routine intraoperative management in noncardiac surgery was shown to be feasible. Compared with conventional haemodynamic management, use of the algorithm significantly reduced length of hospital stay, requirement for ventilation and incidence of prolonged hospital stay, thereby resulting in reduced hospital costs.

Influence of levosimendan on organ dysfunction in patients with severely reduced left ventricular function undergoing cardiac surgery

Objectives Levosimendan is an inotropic drug with organ-protective properties due to its activation of mitochondrial KATP channels. This prospective, randomized, double-blind, placebo-controlled study investigated whether administration of levosimendan prior to cardiopulmonary bypass could reduce organ dysfunction and influence subsequent secondary endpoints. Patients and methods Patients with left ventricular ejection fraction <30% scheduled for elective coronary artery bypass surgery (with or without valve surgery) received either levosimendan (12.5 mg, 0.1 µg kg−1 per min; n = 17) or placebo (n = 16) central venous infusion, immediately after anaesthesia induction, as add-on medication to a goal-orientated treatment algorithm. Results A total of 33 patients completed the study. There were no statistically significant differences in Sequential Organ Failure Assessment scores, survival, haemodynamic parameters, time to extubation, time in intensive care unit, need for haemodialysis or health-related quality-of-life at 6 months post operation. The levosimendan group compared with the placebo group had significantly lower use of epinephrine (35% versus 81%) and nitroglycerine (6% versus 44%) 24 h postoperation, and significantly less frequent serious adverse events (13% versus 47%). Conclusions These preliminary results show that timely perioperative levosimendan treatment is feasible, has a favourable safety profile safe and may help to prevent low cardiac output syndrome. However, organ function was not preserved. Further studies, using larger sample sizes, are required.

Acetylcholinesterase Inhibitors Reduce Neuroinflammation and -Degeneration in the Cortex and Hippocampus of a Surgery Stress Rat Model

Exogenous stress like tissue damage and pathogen invasion during surgical trauma could lead to a peripheral inflammatory response and induce neuroinflammation, which can result in postoperative cognitive dysfunction (POCD). The cholinergic anti-inflammatory pathway is a neurohumoral mechanism that plays a prominent role by suppressing the inflammatory response. Treatments with acetylcholinesterase inhibitors enhance cholinergic transmission and may therefore act as a potential approach to prevent neuroinflammation. In the presence or absence of acetylcholinesterase inhibitors, adult Wistar rats underwent surgery alone or were additionally treated with lipopolysaccharide (LPS). Physostigmine, which can overcome the blood-brain barrier or neostigmine acting only peripheral, served as acetylcholinesterase inhibitors. The expression of pro- and anti-inflammatory cytokines in the cortex, hippocampus, spleen and plasma was measured after 1 h, 24 h, 3 d and 7 d using Real-Time PCR, western blot analysis or cytometric bead array (CBA). Fluoro-Jade B staining of brain slices was employed to elucidate neurodegeneration. The activity of acetylcholinesterase was estimated using a spectrofluorometric method. Surgery accompanied by LPS-treatment led to increased IL-1beta gene and protein upregulation in the cortex and hippocampus but was significantly reduced by physostigmine and neostigmine. Furthermore, surgery in combination with LPS-treatment caused increased protein expression of IL-1, TNF-alpha and IL-10 in the spleen and plasma. Physostigmine and neostigmine significantly decreased the protein expression of IL-1 and TNF-alpha. Neuronal degeneration and the activity of acetylcholinesterase were elevated after surgery with LPS-treatment and reduced by physostigmine and neostigmine. Along with LPS-treatment, acetylcholinesterase inhibitors reduce the pro-inflammatory response as well as neurodegeneration after surgery in the cortex and hippocampus. This combination may represent a tool to break the pathogenesis of POCD.

Oesophageal Doppler and calibrated pulse contour analysis are not interchangeable within a goal-directed haemodynamic algorithm in major gynaecological surgery

BACKGROUND Evidence for the benefit of an intraoperative use of a goal-directed haemodynamic management has grown. We compared the oesophageal Doppler monitor (ODM, CardioQ-ODM™) with a calibrated pulse contour analysis (PCA, PiCCO2™) with regard to assessment of stroke volume (SV) changes after volume administration within a goal-directed haemodynamic algorithm during non-cardiac surgery. METHODS The data were obtained prospectively in patients with metastatic ovarian carcinoma undergoing cytoreductive surgery. During surgery, fluid challenges were performed as indicated by the goal-directed haemodynamic algorithm guided by the ODM. Monitors were compared regarding precision and trending. Clinical characteristics associated with trending were studied by extended regression analysis. RESULTS A total of 762 fluid challenges were performed in 41 patients resulting in 1524 paired measurements. The precision of ODM and PCA was 5.7% and 6.0% (P=0.80), respectively. Polar plot analysis revealed a poor trending between ODM and PCA with an angular bias of -7.1°, radial limits of agreement of -58.1° to 43.8°, and an angular concordance rate of 67.8%. Dose of norepinephrine (NE) (scaled 0.1 µg kg(-1) min(-1)) [adjusted odds ratio (OR) 0.606 (95% confidence interval, CI: 0.404-0.910); P=0.016] and changes in mean arterial pressure (MAP) to a fluid challenge (scaled 10%) [adjusted OR 0.733 (95% CI: 0.635-0.845); P<0.001] were associated with trending between ODM and PCA, whereas there was no relation to type of i.v. solution. CONCLUSIONS Despite a similar precision, ODM and PCA were not interchangeable with regard to measuring SV changes within a goal-directed haemodynamic algorithm. A decrease in interchangeability coincided with increasing NE levels and greater changes of MAP to a fluid challenge.

A Modified Approach to Induce Predictable Congestive Heart Failure by Volume Overload in Rats

The model of infrarenal aortocaval fistula (ACF) has recently gained new interest in its use to investigate cardiac pathophysiology. Since in previous investigations the development of congestive heart failure (CHF) was inconsistent and started to develop earliest 8–10 weeks after fistula induction using a 18G needle, this project aimed to induce a predictable degree of CHF within a definite time period using a modified approach. An aortocaval fistula was induced in male Wistar rats using a 16G needle as a modification of the former 18G needle-technique described by Garcia and Diebold. Results revealed within 28±2 days of ACF significantly increased heart and lung weight indices in the ACF group accompanied by elevated filling pressure. All hemodynamic parameters derived from a pressure-volume conductance-catheter in vivo were significantly altered in the ACF consistent with severe systolic and diastolic left ventricular dysfunction. This was accompanied by systemic neurohumoral activation as demonstrated by elevated rBNP-45 plasma concentrations in every rat of the ACF group. Furthermore, the restriction in overall cardiac function was associated with a β1- and β2-adrenoreceptor mRNA downregulation in the left ventricle. In contrast, β3-adrenoreceptor mRNA was upregulated. Finally, electron microscopy of the left ventricle of rats in the ACF group showed signs of progressive subcellular myocardial fragmentation. In conclusion, the morphometric, hemodynamic and neurohumoral characterization of the modified approach revealed predictable and consistent signs of congestive heart failure within 28±2 days. Therefore, this modified approach might facilitate the examination of various questions specific to CHF and allow for pharmacological interventions to determine pathophysiological pathways.

Salvage surgery due to bowel obstruction in advanced or relapsed ovarian cancer resulting in short bowel syndrome and long-life total parenteral nutrition: surgical and clinical outcome.

Objective Salvage surgery for patients with highly advanced or relapsed epithelial ovarian cancer (EOC) complicated by bowel obstruction and resulting in short bowel syndrome (SBS) constitutes a therapeutic dilemma. Our aim was to evaluate surgical and clinical outcome in these highly palliative situations. Methods We evaluated all patients with EOC who underwent salvage extraperitoneal en bloc intestinal resection with terminal ileostomy or jejunostomy resulting in SBS and total parenteral nutrition owing to bowel obstruction between May 2003 and January 2012 in our institution. Results Thirty-seven patients were identified (median age, 58 years; range, 22–71 years), 3 (8.1%) with primary and 34 (91.6%) with relapsed EOC. Five patients (13.5%) were platinum sensitive. Median residual intestinal length was 70 cm (range, 10–180 cm); 21 patients (56.8%) had a residual intestinal length less than 1 m. Operative 30-day mortality and major morbidity rates were 10% and 51%, respectively. Median overall survival was 5.6 months (range, 0.1–49 months). One-year and 2-year overall survival rates were 18.3% (95% confidence interval, 5.1%–31.5%) and 8.1% (95% confidence interval, 0%–18.0)%, respectively. Within a median follow-up period of 5 months (range, 0.2–49 months), 4 patients (10.8%) are still alive. No significant differences in survival were seen between patients with or without major complications, tumor residuals, or residual intestinal length of less than 1 m versus greater than 1 m. Conclusions Salvage palliative surgery in EOC due to bowel obstruction resulting in SBS and in need of long-life total parenteral nutrition is associated with high morbidity rates and low overall survival. These surgeries should ideally be performed only in a multidisciplinary setting with adequate infrastructure and possibility of home care support. Conservative management should be the route of action in the absence of acute abdomen or intestinal perforation.

Ultrastructural changes associated with myocardial apoptosis, in failing rat hearts induced by volume overload

BACKGROUND Myocardial apoptosis has been discussed to play a pivotal role in the development and progression of congestive heart failure (CHF). However, recently there is doubt on the evidence of myocardial apoptosis in heart failure as information on ultrastructural changes by electron microscopy is still scarce. This project therefore aimed to detect direct morphological evidence of myocardial apoptosis in an experimental heart failure model. METHOD Following IRB approval, an aortocaval fistula (ACF) was induced in male Wistar rats using a 16G needle. 28±2days following ACF rats were examined by hemodynamic measurements, Western blot, immunofluorescence confocal and electron microscopic analysis. RESULTS Within 28±2days of ACF heart (3.8±0.1 vs. 6.6±0.3mg/g) and lung (3.7±0.2 vs. 6.9±0.5mg/g) weight indices significantly increased in the ACF group accompanied by a restriction in systolic (LVEF: 72±2 vs. 39±3%) and diastolic (dP/dtmin.: -10,435±942 vs. -5982±745mmHg/s) function (p<0.01). Activated caspase-3 was significantly increased in failing hearts concomitant with mitochondrial leakage of cytochrome c into the cytosol. Finally, electron microscopy of the left ventricle (LV) of ACF rats revealed pronounced ultrastructural changes in >70% of examined cardiomyocytes, such as nuclear chromatin condensation, myofibril loss and disarray, contour irregularities and amorphous dense bodies, mitochondriosis and damaged cell-cell-contacts between cardiomyocytes. CONCLUSIONS Volume overload induced heart failure is associated with activation of the mitochondrial apoptotic pathway. In addition, electron microscopy of the LV revealed direct ultrastructural evidence of extended myocardial apoptosis in ACF rats.