Kerri M. Robertson

Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery.

Background Intraoperative hypovolemia is common and is a potential cause of organ dysfunction, increased postoperative morbidity, length of hospital stay, and death. The objective of this prospective, randomized study was to assess the effect of goal-directed intraoperative fluid administration on length of postoperative hospital stay. Methods One hundred patients who were to undergo major elective surgery with an anticipated blood loss greater than 500 ml were randomly assigned to a control group (n = 50) that received standard intraoperative care or to a protocol group (n = 50) that, in addition, received intraoperative plasma volume expansion guided by the esophageal Doppler monitor to maintain maximal stroke volume. Length of postoperative hospital stay and postoperative surgical morbidity were assessed. Results Groups were similar with respect to demographics, surgical procedures, and baseline hemodynamic variables. The protocol group had a significantly higher stroke volume and cardiac output at the end of surgery compared with the control group. Patients in the protocol group had a shorter duration of hospital stay compared with the control group: 5 ± 3 versus 7 ± 3 days (mean ± SD), with a median of 6 versus 7 days, respectively (P = 0.03). These patients also tolerated oral intake of solid food earlier than the control group: 3 ± 0.5 versus 4.7 ± 0.5 days (mean ± SD), with a median of 3 versus 5 days, respectively (P = 0.01). Conclusions Goal-directed intraoperative fluid administration results in earlier return to bowel function, lower incidence of postoperative nausea and vomiting, and decrease in length of postoperative hospital stay.

Dexmedetomidine pharmacodynamics: Part II: Crossover comparison of the analgesic effect of dexmedetomidine and remifentanil in healthy volunteers.

Background:Dexmedetomidine is a highly selective &agr;2-adrenoceptor agonist used for short-term sedation of mechanically ventilated patients. The analgesic profile of dexmedetomidine has not been fully characterized in humans. Methods:This study was designed to compare the analgesic responses of six healthy male volunteers during stepwise target-controlled infusions of remifentanil and dexmedetomidine. A computer-controlled thermode was used to deliver painful heat stimuli to the volar side of the forearms of the subjects. Six sequential 5-s stimuli (ranging from 41° to 50°C) were delivered in random order. The recorded visual analog scale was used to fit an Emax model. Results:Compared to baseline, remifentanil infusions resulted in a right shift of the sigmoid curve (increased T50, the temperature producing a visual analog scale score of 50% of the maximal effect, from 46.1°C at baseline to 48.4° and 49.1°C during remifentanil infusions) without a change of the steepness of the curve (identical Hill coefficients &ggr; during baseline and remifentanil). Compared to baseline, dexmedetomidine infusions resulted in both a right shift of the sigmoid curve (increased T50 to 47.2°C) and a decrease in the steepness of the curve (decreased &ggr; from 3.24 during baseline and remifentanil infusions to 2.45 during dexmedetomidine infusions). There was no difference in the pain responses between baseline and after recovery from remifentanil infusions (identical T50 and &ggr;). Conclusion:As expected, dexmedetomidine is not as effective an analgesic as the opioid remifentanil. The difference in the quality of the analgesia with remifentanil may be a reflection of a different mechanism of action or a consequence of the sedative effect of dexmedetomidine.

Intraoperative colloid administration reduces postoperative nausea and vomiting and improves postoperative outcomes compared with crystalloid administration.

The debate over colloid versus crystalloid as the best solution for intraoperative fluid resuscitation is not resolved. Published studies have shown that mortality is not related to the specific fluid used for resuscitation. In addition, the quality of postoperative recovery between colloid and crystalloid has not been well investigated. In a prospective, blinded fashion, we investigated the effects of colloid and crystalloid resuscitation on nausea and vomiting and on the postoperative patient recovery profile. Patients undergoing major elective noncardiac surgery were randomized to receive 6% hetastarch in saline (HS-NS), 6% hetastarch in balanced salt (HS-BS), or lactated Ringer’s solution (LR) on the basis of a fluid administration algorithm. The anesthetic was standardized. Hemodynamic targets included maintenance of arterial blood pressure, heart rate, and urine output within a predefined range. A postoperative morbidity survey was performed at baseline and daily after surgery. Ninety patients participated in the study, with 30 patients in each group. The amounts of study fluid (mean ± sd) administered were 1301 ± 1079 mL, 1448 ± 759 mL, and 5946 ± 1909 mL for the HS-NS, HS-BS, and LR groups, respectively (P < 0.05, HS-NS and HS-BS versus LR). Both the HS-NS and HS-BS (colloid) groups had a significantly less frequent incidence of nausea and vomiting, use of rescue antiemetics, severe pain, periorbital edema, and double vision. We concluded that intraoperative fluid resuscitation with colloid, when compared with crystalloid administration, is associated with an improvement in the quality of postoperative recovery.

Venovenous Bypass in Adult Orthotopic Liver Transplantation: Routine or Selective Use?

BACKGROUND The role of venovenous bypass (VVB) during orthotopic liver transplantation (OLT) remains controversial. The aims of this study were to evaluate the current role of VVB at all major centers in North America, to examine the results of OLT and complications of VVB between two periods with a strict policy for routine versus selective use of VVB, and to review the literature. STUDY DESIGN A survey of 50 major liver transplant centers was conducted using mailed questionnaires. A retrospective chart review was performed for 547 OLT patients having transplantation during two distinct periods with a strict policy for routine versus selective use of VVB at the University of Toronto, Canada, and at Duke University Medical Center, Durham, North Carolina. The literature was reviewed with a focus on the benefits and indications for routine versus selective use of VVB. RESULTS Thirty-eight (76%) of 50 centers responded. Sixteen (42%) of them used VVB routinely, with a reported complication rate of 10-30%. Lymphocele and hematoma were the most common complications, but patients having major vascular injury, air embolism, and death were reported. A recent change to selective use of VVB was reported in 30% of the centers (11 of 38). In the Duke-Toronto series, the complication rates were similar between the two periods, at 13.4% and 18.8%, respectively. The outcome of OLT was not influenced by the policy of routine or selective use of VVB. CONCLUSIONS There is a trend away from the routine use of VVB during OLT. Intraoperative hemodynamic instability during the hepatectomy and a failed trial of hepatic venous occlusion were the most important criteria for using VVB. We conclude that VVB should be used selectively to avoid associated complications and to decrease operative time and costs.

Effect of pH-adjustment of bupivacaine on onset and duration of epidural analgesia in parturients.

Previous studies have reported that elevation of the pH of local anaesthetics is associated with enhanced quality and duration of block. This study investigated the effect, on time to onset and duration of analgesia, of pH adjustment of 0.25 per cent bupivacaine immediately prior to injection into the epidural space in parturients. Addition of 0.1 ml of 8.4 per cent sodium bicarbonate to 20 ml of 0.25 per cent bupivacaine consistently raised the pH of the local anaesthetic from 5.65 to 7.26 (mean values).Thirty parturients received an epidural injection of 8 ml of pH-adjusted 0.25 per cent bupivacaine and a control group of 30 parturients received 8 ml of the standardcommercial preparation of 0.25 per cent bupivacaine. Elevation of the pH of the local anaesthetic significantly increased the speed of onset of analgesia from 6.0 minutes to 3.2 minutes and the duration of analgesia was significantly lengthened from 79.4 minutes to 96.5 minutes. There was no significant influence on time to peak effect, nor on mean maternal plasma levels of bupivacaine.RésuméDes étude préliminaires ont rapporté que l’augmentation du pH des anesthésiques locaux est associée avec une amélioration de la qualité et de la durée du bloc. Cette étude investigue l’effet sur le début d’action et la durée de l’analgésie après ajustement du pH de 0.25 pour cent de bupivacaîne immédiatement avant l’injection dans l’espace épidural chez des femmes à terme. L’addition de 0.1 ml de 8.4 pour cent de bicarbonate de soude à 20 ml de 0.25 pour cent de bupivacaîne augmenta le pH de l’anesthésique local de 5.65 à 7.26 (valeurs moyennes).Trente parturientes ont reçu en injection épidurale 8 ml de bupivacaîne 0.25 pour cent à pH ajusté et un groupe contrôle de 30 parturientes a reçu 8 ml de la solution commerciale standard de préparation de 0.25 pour cent de bupivacaîne. L’augmentation du pH de l’ anesthésique local accéléra significativement le début de l’analgésie de 6.0 minutes à 3.2 minutes ainsi que la durée de l’analgésie qui augmenta significativement de 79.4 minutes à 96.5 minutes. It n’y avail aucune influence significative sur le temps d’effet maximal ni sur le niveau plasmatique moyen maternel de bupivacaîne.

Ionization and Hemodynamic Effects of Calcium Chloride and Calcium Gluconate in the Absence of Hepatic Function

Serial serum ionized calcium concentrations were measured before and after administration of either calcium chloride or calcium gluconate during the anhepatic stage of liver transplantation in 15 patients to determine the release of ionized calcium in the absence of hepatic function. When hypocalcemia (Ca++ less than 0.8 mM) occurred during the anhepatic stage, patients were randomly assigned to treatment with chemically equivalent doses of either calcium chloride (10 mg/kg, n = 8) or calcium gluconate (30 mg/kg, n = 7). Serum concentrations of ionized calcium and citrate, hematocrit, arterial blood gas tensions, acid-base state, and hemodynamic profiles were determined before and up to 10 min after calcium therapy. In both groups of patients initial similar and rapid increases in Ca++ (0.98 +/- 0.14 mM in the calcium chloride group and 1.05 +/- 0.10 mM in the calcium gluconate group) were followed by gradual decreases over the next 10 min. Measured hemodynamic values were similar in the two groups, and neither group showed improvement in cardiovascular function after calcium therapy, possibly because of the decrease in preload that occurred during the anhepatic stage. Equally rapid increases in Ca++ after administration of calcium chloride and gluconate in the anhepatic state suggest that calcium gluconate does not require hepatic metabolism for the release of Ca++ and is as effective as calcium chloride in treating ionic hypocalcemia in the absence of hepatic function.

Anaesthetic management of the brain dead for organ donation.

An increasing number of anaesthetists is being called upon to manage organ donors during organ retrieval procedures. We briefly describe the technical aspects of the surgical procedure together with a guide to the anaesthetic management. The aims of the latter may be summarized as the “Rule of 100”: systolic blood pressure > 100 mmHg, urine output > 100 ml · hr−1, PaO2 > 100 mmHg, haemoglobin concentration > 100 g · L−1. Common management problems hypotension, arrhythmias, diabetes insipidus, oliguria, and coagulopathy) are discussed in detail. The intraoperative management of the brain-dead organ donor provides the anaesthetist with the challenge of a major surgical procedure in a subject with important physiological derangements.RésuméLes anesthésistes sont appelés de plus en plus à devoir s’occuper cles « donneurs » d’organes durant l’opération de prélèvement. Nous décrivons brièvement la technique chirurgicale et proposons un plan d’action pour l’anesthésiste. On peut simplifier en lui proposant de s’en tenir a la «règie des 100»: tension artérielle systolique > 100 mmHg, débit urinaire > 100 ml · h−1, PaO2 > 100 mmHg, hémoglobine > 100 g · L−1. Nous revoyons aussi le traitement des; problemes les plus fréquents: hypotension, arythmie, diabète insipide, oligurie et coagulopathie. Le prélèvement d’organe après mort cérébrate pose à l’anesthésiste, le défi d’une intervention chirurgicale majeure chez un sujet à la physiologie altérée.

Orthotopic liver transplant patients require less postoperative morphine than do patients undergoing hepatic resection.

STUDY OBJECTIVE To compare postoperative morphine use, analgesic efficacy, and side effect profiles in patients following orthotopic liver transplantation (OLTx) and liver resection (LR). DESIGN Retrospective study. SETTING Liver transplant and liver resection surgery at a university hospital. PATIENTS 25 ASA physical status I, II, III, and IV patients undergoing OLTx or liver resection. MEASUREMENTS AND MAIN RESULTS Morphine use was significantly decreased in the OLTx patients at 6,12, 24, 48, and 72 hours following commencement of patient-controlled analgesia. After commencement of patient-controlled analgesia, pain scores were significantly reduced in the OLTx group compared with those in the liver resection group at 6 and 12 hours. CONCLUSIONS Orthotopic liver transplant patients experienced less pain and used less morphine postoperatively than did liver resection patients.

Epidural fentanyl, with and without epinephrine for post-Caesarean section analgesia

Using a double-bolus technique, the efficacy and safety of epidural fentanyl with and without epinephrine 1:400,000 forpost-Caesarean section analgesia was examined in 30 patients. The addition of 25 μg epinephrine to the fentanyl (100 μg) did not potentiate the speed of onset but did significantly prolong the duration of action of the second dose. The only side effect encountered was pruritus, which was significantly increased (from 17-44 per cent) when epinephrine was added. The results indicate a clinical advantage of prolonging the duration of action of fentanyl for post-Caesarean Section analgesia with the addition of epinephrine, but the cumbersome and time-consuming nature of a double-bolus technique limits its clinical value. The relative safety of epidural fentanyl with and without epinephrine was confirmed by the absence of respiratory depression, drowsiness or hypotension in all patients.RésuméL’efficacité et la sécurité du fentanyl en injection épidu-rale associé ou non à l’épinephrine 1:400,000 pour I’analgésie post-césarienne ont été étudiées chez 30 patientes utilisant la technique du double-bolus. L’addition de 25 µg d’épinephrine à 100 µg de fentanyl en injection épidurale n’a pas potentialisé la vitesse du début d’action mais a prolongé significativement la durée d’action de la seconde dose. Le seul effet secondaire encouru était le prurit qui avail significativement augmenté de 17 à 44 pour cent quatid l’épinephrine a été ajoutée. Les résultats indiquent I’avantage clinique de I’addition de l’épinephrine afin de prolonger la dureée d’action du fentanyl administré en épidurale pour Iéanalgésie post-césarienne. Cependant, la technique du double-bolus était encombrante et prenant du temps, limitera sa valeur clinique. La sécurité relative du fentanyl en injection épidurale avec ou sans épinephrine a été confirmée par l’absence de dépression respiratoire, somnolence ou hypotension chez toutes les patientes.

ISOFLURANE ALTERS THE KINETICS OF ORAL CYCLOSPORINE

Cyclosporine is an important immunosuppressive agent often given orally preoperatively to patients undergoing organ transplantation. The aim of the present study was to evaluate the effects of anesthesia on the pharmacokinetics of orally administered cyclosporine. Sixty unanesthetized fasting female Lewis rats were given 25 mg/kg cyclosporine by gastric tube and were then randomized to immediately receive an isoflurane anesthetic (n = 30) or to serve as nonanesthetized controls. At 1, 2, 3, 4, and 6 h after the administration of the cyclosporine, six animals from each group (while still anesthetized for those in the anesthesia group) were killed, and arterial blood and the entire bowel from the esophagogastric junction to the ileocecal junction were removed for measurement of cyclosporine concentrations. A subsequent study with six animals in each group was performed to examine more closely the distribution of cyclosporine in the stomach and small intestine 4 h after the oral dose. In these animals the cyclosporine concentration in the stomach and in five 10-cm-long segments of small bowel was assayed. In all studies of gastrointestinal specimens, the cyclosporine extracted is a combination of that contained in the lumen and the wall.At all times except at 6 h, the blood cyclosporine levels were significantly higher in the control group than in the isoflurane group. Conversely, the amount of cyclosporine in the distal small bowel of control rats was increased as compared with the anesthetized animals. In the animals studied at 4 h, the amount of cyclosporine in the stomach of control rats was significantly lower than that in the anesthetized animals. Conversely, in the first part of the small bowel, the cyclosporine levels were higher in the isoflurane group.We conclude from this study that isoflurane anesthesia reduces the rate of absorption of orally administered cyclosporine primarily by reducing gastric emptying and absorption from the proximal small bowel. Similar results may be found with other anesthetics or other orally administered drugs.