Kathrine Holte

Review of Postoperative Ileus

Postoperative ileus (POI) is an inevitable adverse consequence of surgical procedures. In fact, prolonged POI can lead to patient discomfort, decreased mobility, delayed enteral feeding, and ultimately, prolonged hospitalizations and increased costs. It is believed that POI occurs as a result of inhibitory neural reflexes and inflammatory processes. The use of postoperative opioids also appears to contribute to ileus. Recently, the potential influence of endogenous opioids, in addition to exogenous opioids, on the pathogenesis of ileus has come to light and spurred investigations into new treatment strategies. Over the years, several treatment modalities have become accepted management options for POI; chief among these are nasogastric suction and prokinetic agents. However, data demonstrating that these agents reduce the duration of POI are limited. Of current treatment modalities, use of epidural local anesthetics appears to be the most effective means of reducing POI. Other potentially effective treatments include early enteral feeding and less invasive surgical procedures. Together, these techniques have reduced the length of stay after colonic surgery to 2 to 3 days. Future studies, including those incorporating investigational agents, such as kappa-opioid agonists and peripheral mu-opioid antagonists, into a multimodal regimen, may offer new treatment options to further impact POI duration.

Perioperative single-dose glucocorticoid administration: pathophysiologic effects and clinical implications

The antiinflammatory and immune-modulating effects of glucocorticoids (GCs) have been known for decades and have found extensive therapeutic use in a wide range of diseases of which inflammatory responses are a main feature. A surgical operation elicits a stress response of combined endocrine and inflammatory origin, where an excessive response can lead to increased functional demands on various organic systems, which subsequently might contribute to postoperative morbidity. Increased attention has evolved toward modulating potential deleterious responses. Because GCs might modulate several components of the inflammatory response to surgery, the aim of this review was to update knowledge on the effect of perioperative administration of a single dose of GC on surgical stress responses, postoperative organ dysfunctions, and morbidity in elective surgery with potential implications for clinical practice. Data were obtained by examining randomized clinical trials (RCTs) in which a single dose of GC was administrated systemically in immediate relation to surgery. We do not intend to discuss in depth either the molecular or cellular basis of action of GCs, recently reviewed elsewhere, nor to provide an overview of GC administration in septic or traumatized patients, or in GC-treated surgical patients. A recent metaanalysis concluded that perioperative administration of highdose methylprednisolone was not associated with major side effects. But the trials included consisted of major surgical procedures only, combined with studies in trauma and spinal cord injury, and only methylprednisolone administration was evaluated, including multiple administrations within 3 days of surgery. METHODS A Medline search (1966 to May 2001) was performed to identify all randomized, clinical trials published in English-language journals, in which a single dose of GC was administered systemically and perioperatively (defined as 12 hours before surgery, until the end of surgery; ie, before completion of incision closure) in elective surgical procedures, and where perioperative organ function, morbidity, or both were primary outcomes parameters. The search string consisted of the free text terms “glucocorticoid,” “glucocorticoids,” “dexamethasone,” “methylprednisolone,” “surgery,” and the medical subject headings “glucocorticoids” and “surgical procedures, operative.” All of the above search criteria were combined. The searches were limited to “English” in the language field and “randomized controlled trial” in the publication-type field. Additional studies were identified from review articles and articles cited in original papers. Abstracts, letters to the editor, and nonpublished data were not considered. No related Cochrane review relevant to this subject exists. Studies in patients with chronic GC treatment, patients receiving perioperative immune-suppressive therapy, multiple-dosage GC regimens, and patients receiving a local (at the surgical site) GC application were excluded. We evaluate the evidence of trials comparing GC administration to placebo treatment. In studies evaluating GC treatment against other active treatment and a placebo, only the GC-treated group versus the placebo group was considered.

Monitoring of peri‐operative fluid administration by individualized goal‐directed therapy

Background:  In order to avoid peri‐operative hypovolaemia or fluid overload, goal‐directed therapy with individual maximization of flow‐related haemodynamic parameters has been introduced. The objectives of this review are to update research in the area, evaluate the effects on outcome and assess the use of strategies, parameters and monitors for goal‐directed therapy.

Liberal Versus Restrictive Fluid Administration to Improve Recovery After Laparoscopic Cholecystectomy: A Randomized, Double-Blind Study

Objective:The objective of this study was to investigate the effects of 2 levels of intraoperative fluid administration on perioperative physiology and outcome after laparoscopic cholecystectomy. Summary Background Data:Intraoperative fluid administration is variable as a result of limited knowledge of physiological and clinical effects of different fluid substitution regimens. Methods:In a double-blind study, 48 ASA I–II patients undergoing laparoscopic cholecystectomy were randomized to 15 mL/kg (group 1) or 40 mL/kg (group 2) intraoperative administration of lactated Ringer’s solution (LR). All other aspects of perioperative management as well as preoperative fluid status were standardized. Primary outcome parameters were assessed repeatedly for the first 24 postoperative hours and included pulmonary function (spirometry), exercise capacity (submaximal treadmill test), cardiovascular hormonal responses, balance function, pain, nausea and vomiting, recovery, and hospital stay. Results:Intraoperative administration of 40 mL/kg compared with 15 mL/kg LR led to significant improvements in postoperative pulmonary function and exercise capacity and a reduced stress response (aldosterone, antidiuretic hormone, and angiotensin II). Nausea, general well-being, thirst, dizziness, drowsiness, fatigue, and balance function were also significantly improved, as well as significantly more patients fulfilled discharge criteria and were discharged on the day of surgery with the high-volume fluid substitution. Conclusions:Intraoperative administration of 40 mL/kg compared with 15 mL/kg LR improves postoperative organ functions and recovery and shortens hospital stay after laparoscopic cholecystectomy.

Physiologic effects of bowel preparation.

PURPOSE:Despite the universal use of bowel preparation before colonoscopy and colorectal surgery, the physiologic effects have not been described in a standardized setting. This study was designed to investigate the physiologic effects of bowel preparation.METHODS:In a prospective study, 12 healthy volunteers (median age, 63 years) underwent bowel preparation with bisacodyl and sodium phosphate. Fluid and food intake were standardized according to weight, providing adequate calorie and oral fluid intake. Before and after bowel preparation, weight, exercise capacity, orthostatic tolerance, plasma and extracellular volume, balance function, and biochemical parameters were measured.RESULTS:Bowel preparation led to a significant decrease in exercise capacity (median, 9 percent) and weight (median, 1.2 kg). Plasma osmolality was significantly increased from 287 to 290 mmol kg−1, as well as increased phosphate and urea concentrations, whereas calcium and potassium concentrations decreased significantly after bowel preparation. No differences in plasma or extracellular volumes were seen. Orthostatic tolerance and balance function did not change after bowel preparation.CONCLUSIONS:Bowel preparation has significant adverse physiologic effects, which may be attributed to dehydration. The majority of these findings is small and may not be of clinical relevance in otherwise healthy patients undergoing bowel preparation and following recommendations for oral fluid intake.

Postoperative ileus: Progress towards effective management

The pathogenesis of postoperative ileus (PI) is multifactorial, and includes activation of inhibitory reflexes, inflammatory mediators and opioids (endogenous and exogenous). Accordingly, various strategies have been employed to prevent PI. As single-modality treatment, continuous postoperative epidural analgesia including local anaesthetics has been most effective in the prevention of PI. Choice of anaesthetic technique has no major impact on PI. Minimally invasive surgery reduces PI, in accordance with the sustained reduction in the inflammatory responses, while the effects of early institution of oral nutrition on PI per se are minor. Several pharmacological agents have been employed to resolve PI (propranolol, dihydroergotamine, neostigmine, erythromycin, cisapride, meto-clopramide, cholecystokinin, ceruletide and vasopressin), most with either limited effect or limited applicability because of adverse effects. The development of new peripheral selective opioid antagonists is promising and has been demonstrated to shorten PI significantly. A multi-modal rehabilitation programme including continuous epidural analgesia with local anaesthetics, enforced nutrition and mobilisation may reduce PI to 1–2 days after colonic surgery.

Effects of gabapentin in acute inflammatory pain in humans

Background and Objectives The aim of the study was to examine the analgesic effects of the anticonvulsant, gabapentin, in a validated model of acute inflammatory pain. Methods Twenty-two volunteers were investigated in a double-blind, randomized, placebo-controlled cross-over study. Gabapentin 1,200 mg or placebo was given on 2 separate study days. Three hours after drug administration, a first-degree burn injury was produced on the medial aspect of the nondominant calf (12.5 cm2, 47°C for 7 minutes). Quantitative sensory testing (QST) included pain ratings to thermal and mechanical stimuli (visual analog scale [VAS]), assessments of thermal and mechanical detection thresholds, and areas of secondary hyperalgesia. Side effects drowsiness and postural instability were assessed by subjective ratings (VAS). Results The burn injury induced significant primary and secondary hyperalgesia (P < .0001). Gabapentin diminished the decrease in mechanical pain threshold in the burn area (P = .04) and reduced secondary hyperalgesia, but the reduction was not significant (P = .06). Heat pain thresholds, pain during the burn, and mechanical pain in the area of secondary hyperalgesia were not significantly changed by gabapentin (P < .2). Ratings of drowsiness and unsteadiness during walking were significantly higher for gabapentin than for placebo (P < .05). Conclusions The study indicates that gabapentin has no analgesic effect in normal skin, but may reduce primary mechanical allodynia in acute inflammation following a thermal injury. These observations suggest a clinical potential of gabapentin in the treatment of postoperative pain.

Epidural Anesthesia, Hypotension, and Changes in Intravascular Volume

BackgroundThe most common side effect of epidural or spinal anesthesia is hypotension with functional hypovolemia prompting fluid infusions or administration of vasopressors. Short-term studies (20 min) in patients undergoing lumbar epidural anesthesia suggest that plasma volume may increase when hypotension is present, which may have implications for the choice of treatment of hypotension. However, no long-term information or measurements of plasma volumes with or without hypotension after epidural anesthesia are available. MethodsIn 12 healthy volunteers, the authors assessed plasma (125I-albumin) and erythrocyte (51Cr-EDTA) volumes before and 90 min after administration of 10 ml bupivacaine, 0.5%, via a thoracic epidural catheter (T7–T10). After 90 min (t = 90), subjects were randomized to administration of fluid (7 ml/kg hydroxyethyl starch) or a vasopressor (0.2 mg/kg ephedrine), and 40 min later (t = 130), plasma and erythrocyte volumes were measured. At the same time points, mean corpuscular volume and hematocrit were measured. Systolic and diastolic blood pressure, heart rate, and hemoglobin were measured every 5 min throughout the study. Volume kinetic analysis was performed for the volunteers receiving hydroxyethyl starch. ResultsPlasma volume did not change per se after thoracic epidural anesthesia despite a decrease in blood pressure. Plasma volume increased with fluid administration but remained unchanged with vasopressors despite that both treatments had similar hemodynamic effects. Hemoglobin concentrations were not significantly altered by the epidural blockade or ephedrine administration but decreased significantly after hydroxyethyl starch administration. Volume kinetic analysis showed that the infused fluid expanded a rather small volume, approximately 1.5 l. The elimination constant was 56 ml/min. ConclusionsThoracic epidural anesthesia per se does not lead to changes in blood volumes despite a reduction in blood pressure. When fluid is infused, there is a dilution, and the fluid initially seems to be located centrally. Because administration of hydroxyethyl starch and ephedrine has similar hemodynamic effects, the latter may be preferred in patients with cardiopulmonary diseases in which perioperative fluid overload is undesirable.

Epidural analgesia and risk of anastomotic leakage.

Background and Objectives Based on case reports of early anastomotic leakage in patients receiving epidural analgesia with local anesthetic and data to document a stimulatory effect of epidural block on gastrointestinal motility, it has been suggested that continuous infusion of epidural local anesthetic may lead to an increased incidence of anastomotic leakage. Therefore, we examined the association between continuous epidural local anesthetic and anastomotic leakage by reviewing the literature. Methods Review of controlled, randomized clinical trials aiming to investigate postoperative complications in which continuous postoperative epidural local anesthetic was administered in patients scheduled for colorectal surgery with an anastomosis. Data were obtained from a Medline search (1966-May 2000), previous review articles, references cited in original papers, and personal communication with investigators. Twelve trials including a total of 562 patients met the inclusion criteria. Results Sixteen of 266 patients (6.0%, 95% confidence interval [CI]: 3.5% to 9.6%) receiving postoperative epidural local anesthetic or epidural local anesthetic-opioid mixtures developed anastomotic leakage, compared with 10 of 296 patients (3.4%, 95% CI: 1.6% to 6.1%) receiving epidural or systemic opioid-based analgesia (P > .05 between groups, Fisher’s test). The risk of overlooking a significant difference (type II error) was approximately 67% (power: 33%). Studies including more than 1,037 patients in each group are needed to demonstrate an increased risk of anastomotic leakage from 3.4% to 6.0% with 80% power and 2α = 0.05. There was no significant difference (P > .05 between groups, Fisher’s test) between subgroups of study design: Epidural local anesthetic versus systemic or epidural opioid, or epidural local anesthetic-opioid mixtures versus systemic or epidural opioid. Conclusions So far, there is no statistically significant evidence from randomized trials to indicate epidural analgesia with local anesthetic to be associated with an increased risk of anastomotic breakdown. However, relatively few patients have been included in randomized trials, indicating a need for more studies to secure valid conclusions.

Liberal versus restrictive fluid management in knee arthroplasty : A randomized, double-blind study

BACKGROUND:There are few data describing the relationship between amount of perioperative fluid and organ function. In this study we investigated the effects of two levels of intravascular fluid administration (“liberal” versus “restrictive”) in knee arthroplasty on physiological recovery as the primary outcome variable. METHODS:In a double-blind study, 48 ASA I–III patients undergoing fast-track elective knee arthroplasty were randomized to restrictive or liberal perioperative intravascular fluid administration. Patients received a fixed rate infusion of Ringer’s lactate solution with a standardized volume of colloid. All other aspects of perioperative management (including anesthesia, preoperative fluid status, and postoperative management) were standardized. Primary outcome variables included pulmonary function (spirometry), exercise capacity (“timed up and go” test), coagulation (Thrombelastograph®), postoperative hypoxemia (nocturnal pulse oximetry), postoperative ileus (defecation), and subjective patient recovery (visual analog scales). Hospital stay and complications were also noted. RESULTS:Fluid guidelines were followed strictly in all patients. Liberal (median 4250 mL, range 3150–5200 mL) compared with restrictive (median 1740 mL, range 1100–2165 mL) intravascular fluid administration led to improved pulmonary function 6 h postoperatively, significant hypercoagulability 24–48 h postoperatively, and reduced incidence of vomiting. There were no overall differences in the other assessed perioperative physiological recovery variables (postoperative hypoxemia, exercise capacity or subjective patient recovery variables). No difference was found in hospital stay (median 4 days in both groups, not significant). CONCLUSION:A liberal compared to a restrictive intravascular fluid regimen may lead to significant hypercoagulability and a reduction in vomiting, but without differences in other recovery variables or hospital stay after fast-track knee arthroplasty.