Continuous postoperative infusion of a regional anesthetic after an amputation of the lower extremity. A randomized clinical trial

We performed a prospective, randomized clinical trial to determine whether continuous infusion of bupivacaine hydrochloride decreased the use of narcotics for the relief of pain after an amputation. Twenty-one patients who were to have an amputation of the lower extremity because of ischemic necrosis secondary to peripheral vascular disease were divided into two groups with use of a table of random numbers. Group A (the treatment group) included nine patients who were to have a transtibial amputation, one patient who was to have a disarticulation at the knee, and one patient who was to have a transfemoral amputation. Group B (the control group) included seven patients, two patients, and one patient, respectively. After the amputation had been performed, a Teflon catheter was placed adjacent to the transected end of the sciatic or posterior tibial nerve. Postoperatively, the patients received continuous infusion of either bupivacaine (Group A) or normal saline solution (Group B) for seventy-two hours. Intravenous administration of morphine with use of a patient-controlled pump also was permitted during this period. The amount of morphine that was used was recorded meticulously. The patients in Group A used less morphine during the first and second days after the operation than did those in Group B. There was no difference between the groups with regard to the amount of morphine used on the third postoperative day. Over-all, eleven of fourteen patients who completed questionnaires reported a decrease in pain between the three and six-month evaluations. We concluded that continuous perineural infusion of an anesthetic appears to be a safe, effective method for the relief of postoperative pain but that it does not prevent residual or phantom-limb pain in patients who have had an amputation of the lower extremity because of ischemic changes secondary to peripheral vascular disease.     

Residual pneumoperitoneum: a cause of postoperative pain after laparoscopic cholecystectomy

After laparoscopic cholecystectomy, residual gas is inevitably retained in the peritoneal cavity. An active attempt is not always made to remove it. Using a double-blind prospective protocol in 40 healthy patients, we evaluated the effect of residual pneumoperitoneum on post-laparoscopic cholecystectomy pain intensity. On completion of surgery, prior to removal of the surgical instruments, the patients were randomly divided into two groups: in the active aspiration (AA) group an active attempt was made to remove as much gas as possible from the peritoneal cavity, while in the nonactive aspiration (NAA) group no such effort was made. Postoperative pain was assessed hourly over a 4-h period with a visual analog scale (VAS) and a patient-controlled analgesia (PCA) device. During the first postoperative hour, the NAA patients made significantly (P < 0.05) more demands (mean +/- SD) for morphine than those in the AA group (31.3 +/- 26.2 vs 15.3 +/- 15.7) and also received a borderline significantly (P = 0.056) larger dose (mean +/- SD) of PCA morphine (3.9 +/- 1.9 mg vs 2.7 +/- 1.3 mg). The VAS scores (mean +/- SD) over the 4-h study period were similar in both groups, being high during the first postoperative hour (AA = 5.1 +/- 2.1 vs NAA = 6.1 +/- 2.2) and then decreasing. We conclude that residual pneumoperitoneum is a contributing factor in the etiology of postoperative pain after laparoscopic cholecystectomy.     

Factors that may increase morbidity in a model of intra-abdominal contamination caused by gallstones lost in the peritoneal cavity

OBJECTIVE: To assess the effect of intraperitoneal gallstones with and without Escherichia coli and sterile bile on the incidence of intraperitoneal complications in mice. DESIGN: Prospective randomised study. SETTING: Teaching hospital, Turkey. MATERIAL: 180 Swiss albino mice in five groups, n = 20 in the control group, and n = 40 in each of the experimental groups. INTERVENTIONS: Group A laparotomy alone (controls); group B, laparotomy amd intraperitoneal instillation of E. coli 4 x 10(6) 0.1 ml; group C, laparotomy and insertion of sterilised gallstones; group D, laparotomy, insertion of gallstones and instillation of E. coli 4 x 10(6) 0.1 ml; and group E, laparotomy, insertion of gallstones, and instillation of E. coli 4 x 10(6) 0.1 ml and sterile bile 0.1 ml. A quarter of each group was killed after 1, 2, 4, and 8 weeks. MAIN OUTCOME MEASURES: Intra-peritoneal abscesses, adhesions, perforations, fistula, or obstruction. RESULTS: No mice died. Adhesions were found in 3(15%), 7(18%), 30(75%), 25(63%), and 24(60%) in the five groups, respectively. No mice in groups A, B, or C developed an abscess, but 8 did in each of groups D and E (20%). One mouse in group D developed obstruction. Logistic regression showed that abscess formation was significantly increased by the addition of gallstones and E. coli to the peritoneal cavity (p < 0.001) but the addition of bile had no effect. Gallstones increased the rate of adhesions more than nine fold (p < 0.001) but E. coli with or without bile had no effect (p = 0.75). CONCLUSIONS: Free gallstones within the peritoneal cavity with or without E. coli or sterile bile, or both, increased the rate of formation of both abscesses and adhesions in mice. These results suggest that efforts should be made retrieve gallstones that are dropped into the peritoneal cavity during laparoscopic cholecystectomy, particularly in patients with acute cholecystitis.     

Failure of nocturnal changes in growth hormone to alter carbohydrate tolerance the following morning

To determine whether the increases in growth hormone that occur during sleep alter carbohydrate tolerance the following morning, two groups of volunteers were studied on two occasions. In one group saline alone was injected and infused (i.e. no octreotide) on one occasion and on the other octreotide was injected at 23.00 hours to inhibit endogenous growth hormone secretion followed by saline infusion to create a state of relative nocturnal growth hormone deficiency. In the other group the octreotide injection was followed on one occasion by a constant growth hormone infusion designed to maintain growth hormone concentrations at "basal" levels throughout the night whereas on the other it was followed by a constant infusion plus two supplemental growth hormone infusions given at midnight and 02.30 hours to mimic the normal nocturnal rise in growth hormone. The next morning, subjects were fed a radiolabelled mixed meal. The differences in the nocturnal growth hormone concentrations had no effect on the glucose, insulin, C-peptide and glucagon concentrations following breakfast ingestion nor did they alter postprandial rates of glucose production, disappearance or substrate oxidation. Thus, the normal nocturnal rise in growth hormone does not appear to be an important regulator of carbohydrate tolerance the following morning.     

Evaluation of the synergism between ketorolac and morphine in the treatment of postoperative pain

BACKGROUND: The aim of the study is to determine what concentration of ketorolac and morphine administered together i.v. achieve best synergic effect between NSAID antiinflammatory and opioids analgesic properties. DESIGN: Randomized comparative study was carried out on 180 patients, ASA II-IV, undergoing major general surgery, in an University Clinic. METHODS: Postoperative pain therapy by i.v. PCA: group 1 morphine 0.75 mg.ml + ketorolac 0.75 mg.ml; group 2 morphine 0.50 mg.ml + ketorolac 1.50 mg.ml; group 3 morphine 0.25 mg.ml + ketorolac 1.50 mg.ml; in saline solution. Initial bolus: 2 ml. Continuous infusion 1.5 ml.h. Demand bolus: 0.2 ml. Lockout time: 30 minutes. Evaluations included: pain intensity (T0, T3, T18); total amount of infused drugs (T18); number of valid demands and attempts (T18); amount of autoadministered analgesic drugs in percent of highest available amount (T18); side effects (T18); patient's judgment. DATA ANALYSIS: ANOVA and Student's "t"-test. RESULTS: A statistically significant reduction of pain intensity was found after 3 and 18 hours in the three groups, no differences were found among the groups. Group 2 required an amount of autoadministered drugs significantly lower than other groups. Rare side effects. Patient's judgment was generally positive. CONCLUSIONS: Results suggest a greater synergetic effect between morphine and ketorolac in concentrations used in group 2.     

Pretreatment with topical 60% lidocaine tape reduces pain on injection of propofol

We determined whether pretreatment with topical 60% lidocaine tape reduced the incidence of pain on injection of propofol compared with mixing intravenous lidocaine with propofol. In a randomized, double-blind trial, 90 patients were allocated to one of three groups: pretreatment with a bioocclusive dressing and administration of a premixed solution of propofol 180 mg and 2 mL of normal saline (Group A); pretreatment with 60% lidocaine tape and a premixed solution of propofol and normal saline (Group B); or pretreatment with a bioocclusive dressing and a premixed solution of propofol 180 mg and lidocaine 40 mg (Group C). The incidences of pain in Groups A, B, and C were 86.7%, 33.4%, and 20%, respectively. Group B and Group C had a significantly lower incidence of pain than Group A. There was no significant difference in the incidence of pain between Group B and Group C. There was no significant difference in the distribution of site of pain on injection of propofol among the three groups. Pretreatment with topical 60% lidocaine tape reduced the incidence of pain on injection of propofol similar to that of intravenous lidocaine mixed with propofol. IMPLICATIONS: Pretreatment with topical 60% lidocaine tape reduces the pain associated with injection of propofol, a frequently used intravenous anesthetic. This approach should increase patient comfort during induction of anesthesia.     

Transcapillary ultrafiltration and peritoneal equilibration test in pediatric patients

The usefulness of the peritoneal equilibration test (PET) in children is unknown. The relationship between transcapillary ultrafiltration and PET was investigated in order to evaluate the usefulness of PET in children. PET was performed on 14 patients undergoing peritoneal dialysis. Their age and bodyweight ranged from 3.8 to 23.6 years and 10.2 to 55.8 kg, respectively. The patients were divided into two groups according to bodyweight; group A patients weighed < or = 40 kg (n = 7) and group B patients weighed > 40 kg (n = 7). There was no significant difference in the mean infusion volume per bodyweight between the two groups, but the mean infusion volume per body surface area was smaller in group A than in group B. Group A showed a more rapid equilibration of dialysate glucose and creatinine than group B. Higher normalized mass transfer area coefficients were evident in group A. In spite of the lower effective glucose gradient in group A, the transcapillary ultrafiltration capacity (TUFC) showed no difference between the two groups. When the slope indices of the regression equations between the two groups were compared, the slopes of the regression in the relationship between TUFC and dialysate (D) ratios D/Do glucose or D/P creatinine in group A were steeper than those in group B. Results of the present study indicate that the larger peritoneal area to infusion volume in patients with smaller body size results in both a rapid equilibration of solutes and sufficient transcapillary ultrafiltration.     

Patency of 24-gauge peripheral intermittent infusion devices: a comparison of heparin and saline flush solutions

The purpose of this study was to compare the effectiveness of heparin and normal saline flush solutions in maintaining the patency of 24-gauge peripheral intermittent infusion devices (PIIDs). A prospective, non-randomized, sequential, blinded study design was conducted on a pediatric and a neonatal intensive care unit. The sample consisted of 134 catheters in 61 patients. Heparin and saline flush groups were similar for age, PIID placement site, irritating substances infused, and initial IV function. The median duration of catheters flushed with heparin was 42 hours and with saline was 35.3 hours. Kaplan-Meier Survival Analysis indicated that the duration of catheters flushed with heparin was significantly longer than those flushed with saline (p = .02). More catheters flushed with saline were removed because of problems (p = .027). Results of this study suggest that heparin is more effective than saline in maintaining the patency of small, 24-gauge catheters.     

Prevention of bleeding after cardiopulmonary bypass with high-dose tranexamic acid. Double-blind, randomized clinical trial

This prospective, double-blind, randomized trial assessed the effectiveness of high-dose tranexamic acid given in the preoperative period on blood loss in patients undergoing cardiopulmonary bypass. One hundred fifty patients scheduled to undergo cardiac operations with cardiopulmonary bypass were randomized into three groups of equal size. The first group received 10 gm of tranexamic acid intravenously over 20 minutes before sternotomy and a placebo infusion over 5 hours. The second group received 10 gm of tranexamic acid over 20 minutes and then another 10 gm infused intravenously over 5 hours. The control group received a placebo bolus and a placebo infusion over 5 hours (0.9% normal saline solution). The blood loss after the operation was measured at 6 hours and 24 hours. The homologous blood and blood products given during and up to 48 hours after operation were recorded. Eighteen percent of the control group patients shed more than 750 ml blood in 6 hours compared with only 2% in both tranexamic acid groups. Patients who shed more than 750 ml blood required 93% more red blood cell transfusions than patients without excessive bleeding. Tranexamic acid (10 gm) given intravenously in the period before cardiopulmonary bypass reduced blood loss over 6 hours by 50% and over 24 hours by 35%. Continued tranexamic acid infusion (10 gm over 5 hours) did not reduce bleeding further. There was no difference in the coagulation profile before operation between patients with and without excessive bleeding. However, coagulation tests done in the postoperative period indicated ongoing fibrinolysis and platelet dysfunction in patients with excessive bleeding.     

Effects of the stable prostacyclin analogue iloprost on mesenteric blood flow in porcine endotoxic shock

OBJECTIVE: To determine the effects of the stable prostacyclin analog, iloprost, in a porcine model of endotoxin-induced mesenteric ischemia. DESIGN: Prospective, experimental, randomized, controlled study. SETTING: Animal research laboratory at a university medical center. INTERVENTIONS: Pigs were randomized to receive a constant infusion of iloprost (0.18 microg/kg/min) or an equivalent amount of carrier solution (normal saline) 30 mins before being infused with endotoxin (100 microg/kg over 1 hr). The infusion with iloprost or carrier solution was continued for the duration of the experiment. MEASUREMENTS AND MAIN RESULTS: Twelve pigs (six per group), weighing between 20 and 22 kg, underwent laparotomy during which a magnetic flowprobe was placed around the superior mesenteric artery and an ileal tonometer was inserted. Thirty minutes before they were infused with endotoxin, the animals were randomized to receive intravenous iloprost or normal saline. Endotoxin was infused centrally over a 60-min period. Animals received normal saline at a rate of 1.2 mL/kg/min which was begun at the start of the endotoxin infusion. Data were measured at the end of the endotoxin infusion (E60) and 1 hr later (E120). Mean arterial pressure was not affected by the dosage of iloprost used in this experiment. After resuscitation, the cardiac output returned to baseline in the iloprost-treated group but remained decreased in the control group (2.6 +/- 0.5 vs. 1.6 +/- 0.4 L/min). Superior mesenteric blood flow increased 34% above baseline levels in animals pretreated with iloprost (from 363 +/- 85 to 485 +/- 81 mL/min). The superior mesenteric PCO2 was significantly higher (53 +/- 9 vs. 40 +/- 5 torr; 7.1 +/- 1.2 vs. 5.3 +/- 0.7 kPa) and the ileal intramucosal pH was significantly lower (7.07 +/- .28 vs. 7.44 +/- .23) in the control group than in the iloprost-treated group. CONCLUSIONS: Pretreatment with intravenous iloprost effectively increased intestinal blood flow in this model of endotoxin-induced mesenteric ischemia. This action of the drug resulted in an attenuation of ileal intracellular acidosis. Since low-dose iloprost had no effect on mean arterial pressure, it may be a useful adjunct in the treatment of sepsis and septic shock.     

The effect of plasma free fatty acids and long-chain triglycerides on glucose metabolism in uncomplicated falciparum malaria

To investigate the therapeutic potential of increased plasma free fatty acid (FFA) and triglyceride concentrations in hypoglycaemic patients receiving quinine, 32 untreated Thai adults with uncomplicated falciparum malaria were allocated at random to one of 4 regimens: 2 mg/kg/min dextrose infused over 60 min either alone (group A) or with a prior injection of 5000 units of heparin and simultaneous Intralipid infusion (group C), or 4 min/kg/min dextrose alone (group B) or with heparin and Intralipid (group D). Quinine (10 mg/kg) was also infused over 60 min in all cases. In patients of groups A and C, mean changes in plasma glucose concentrations from the beginning to the end of the infusion were 0.1 (SD 0.8) and 1.0 (SD 0.7) mmol/L respectively (P = 0.015). In groups B and D, plasma glucose increased by 1.8 (SD 1.2) and 2.2 (SD 0.4) mmol/L respectively (P < 0.5). Plasma FFA levels fell by approximately 50% during the infusion in groups A and B but increased by a similar percentage in groups C and D. Despite significant mean increases in plasma insulin during the infusion (from 12.2 milliunits (mu)/L in group A to 38.8 mu/L in group D), no rebound hypoglycaemia was observed in any patient during the ensuing 7 h. These data suggest that the glycaemic response to dextrose given at high rates, which match average glucose utilization in a severely ill patient with malaria, is not augmented by increased plasma FFA and long-chain triglycerides. However, this strategy increases the glycaemic efficacy of lower dextrose infusion rates and the combination could, therefore, reduce the volumes of hypertonic dextrose required to prevent hypoglycaemia in severely ill patients in whom optimal fluid balance is crucial.     

Influence of light dark cycles on estradiol-17 beta induced luteinizing hormone patterns of the prepuberal gilt

Two groups of Yorkshire gilts (110 d of age) were maintained in two light regimens. Both light regimens consisted of 14 h of light and 10 h of darkness, but were 180 degrees out of phase. Gilts in Group 1 received light from 1200 to 0200 and gilts in Group 2 from 2400 to 1400. At approximately 140 d of age each group was divided into four subgroups of eight gilts each (1A, 1B, 1C, 1D or 2A, 2B, 2C, 2D). All gilts were blood sampled at 2-h intervals for 5 d commencing on d 142. The four subgroups received a single injection of estradiol (15 micrograms/kg body weight) on d 143 at either 2400 (A), 0600 (B), 1200 (C), or 1800 (D). For pigs in Groups 1A and 1D, the injection of estradiol coincided with the animals' "subjective day" and the injections given to Groups 1B and 1C with their "subjective night." When estradiol-17 beta (E2) was administered to the gilts during their subjective day the LH profile showed one peak, whereas when E2 was administered during dark hours the profile exhibited two peaks (P < .0001). In Group 2 for which the light cycle was reversed, the well-defined spikes of LH were found to coincide with the injections of estradiol administered during the dark hours. Smaller biphasic peaks of LH occurred when injections of estradiol coincided with the light hours.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mesh configurations in laparoscopic extraperitoneal herniorrhaphy. A comparison of techniques

BACKGROUND: Laparoscopic total extraperitoneal (TEP) hernia repair utilizes slit mesh that is placed around the spermatic cord to secure the prosthesis and prevent recurrence. Because of concern that encircling of the cord might increase pain and morbidity, we compared patients with mesh repairs using encircled and nonencircled techniques. METHODS: The 191 male patients who underwent bilateral TEP repairs were divided into three groups. In 100 consecutive patients (group A), the slit mesh was closed around both spermatic cords; in 56 patients (group B), the slit mesh was tucked under the spermatic cords but not closed; in 35 consecutive patients (group C), the slit was closed around one cord and tucked under the other, in a randomized fashion. RESULTS: The groups had similar operative times (A: 83 +/- 25 min; B: 79 +/- 21; C; 77 +/- 24), use of pain medication (A: 2.7 +/- 2.5 days; B: 2.4 +/- 1.9; C: 3.1 +/- 2.4), and recovery before return to work (A: 7.9 +/- 7.0 days; B: 8.2 +/- 6.1; C: 6.7 +/- 4.8). The incidence of indirect hernias was similar in all groups. Complication rate was 20% in A, 20% in B, and 14% in C (p = NS). Chronic pain was more frequent in A (A: 6, B: 0, p = 0. 06). In group C, fluid collections were more common on the closed side (closed: 3, tucked: 0; p = 0.08). There were no recurrences in any group. CONCLUSIONS: Closing the slit around the spermatic cord in laparoscopic inguinal hernia repair is not essential for prevention of early recurrence. Fluid collections tended to be more frequent when the mesh was closed around the cord, and chronic pain was more frequent in the group with closed mesh bilaterally.     

Liver as a focus of impaired oxygenation and cytokine production in a porcine model of endotoxicosis

OBJECTIVES: To determine whether the liver is a focus of insufficient oxygenation and whether liver is a source of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in a porcine model of endotoxicosis. DESIGN: In vivo, prospective, controlled, repeated-measures, experimental study. SETTING: Experimental physiology laboratory in a university. SUBJECTS: Juvenile pigs, weighing 22 to 35 kg. INTERVENTIONS: Catheters for blood sampling were inserted into the carotid artery, portal vein, hepatic vein, and pulmonary artery of anesthetized animals. Ultrasonic flow probes were placed on the portal vein and the hepatic artery. During surgery, normal saline was infused intravenously at 25 mL/kg/hr. Following stabilization, animals were allocated randomly to one of two groups. The endotoxemic group (n = 6) received 50 mg/kg of purified Escherichia coli lipopolysaccharide infused into the external jugular vein over 1 hr. The control group (n = 6) received a sham saline infusion infused over 1 hr. Once the endotoxin or sham infusion was initiated, the rate of the intravenous saline infusion was increased to 48 mL/kg/hr for the remainder of the experiment. Measurements were obtained before the endotoxin or sham infusion, immediately after the infusion, and every 30 mins thereafter for 4 hrs. MEASUREMENTS AND MAIN RESULTS: Blood gases, lactate, and bioactive TNF and IL-6 concentrations were measured from the carotid artery, portal vein, hepatic vein, and pulmonary artery. The porcine model is characterized by systemic hypotension, pulmonary hypertension, and maintenance of cardiac output. Despite decreased hepatic oxygen delivery in endotoxemic animals (p < .02), there was no change in hepatic oxygen consumption compared with controls. Throughout the experiment, there was net hepatic consumption of lactate in both groups. There was no significant hepatic production (or consumption) of TNF or IL-6 in either group. CONCLUSIONS: In this porcine model of endotoxicosis, there is a reduction of hepatic oxygen delivery but dysoxia is not present. The liver is not a source of TNF or IL-6 in this model of endotoxicosis.     

Posterior approaches in groin hernia repair with prosthesis: open or closed

Laparoscopic herniorraphies have been used to reduce the pain and convalescence associated with open approaches. However, there is still not any consensus of the best approach. We compared open preperitoneal and laparoscopic total extraperitoneal approaches in groin hernia repair. METHODS: Thirty-two patients underwent open preperitoneal herniorraphy (Group I) and other 32 patients underwent total extraperitoneal repair (Group II). Time of surgery was noted. Visual Analogue Scale (VAS) was applied to evaluate the postoperative pain intensity. RESULTS: Operation time was 35 (20-65) minutes in Group I and 58 (40-85) minutes in Group II (p < 0.05). The difference of complication ratios between two groups was not significant. Laparoscopic approach was associated with less pain within postoperative 24 hours as compared to the open technique. However, after the first postoperative day, there was no longer statistically significant difference between both groups. No recurrence has yet been seen in follow-up period of 15 (4-24) months. CONCLUSION: Laparoscopic herniorraphy is associated with better results in term of postoperative pain within the first 24 hours as compared to open technique.     

The clinical characteristics of intraoral herpes simplex virus infection in 52 immunocompetent patients

OBJECTIVES: To determine if nonsteroidal anti-inflammatory drugs provide adequate pain control for patients having laparoscopic hernia repair and to compare the effectiveness of ketorolac tromethamine with ibuprofen in reducing postoperative laparoscopic hernia pain. DESIGN AND SETTING: Prospective double-blind randomized study at a 100-bed community hospital. PATIENTS: Seventy patients ranging in age from 16 to 83 years scheduled for elective laparoscopic inguinal hernia repair. INTERVENTIONS: Patients undergoing laparoscopic hernia repair were enrolled in a double-blind randomized study to compare the 2 treatments. Group 1 received a placebo capsule 1 hour before surgery and ketorolac tromethamine, 60 mg intravenously, at the time of trocar insertion. Group 2 received ibuprofen, 800 mg an hour before surgery, and isotonic sodium chloride solution, 2 mL intravenously, at the time of trocar insertion. In addition, all patients received local infiltration of 30 mL of bupivacaine hydrochloride into their trocar sites. All patients were discharged within 5 hours of the operation and were instructed to take 400 mg of ibuprofen orally every 4 hours for 24 hours whether or not they were experiencing pain. A 24-hour supply of ibuprofen was provided to all study patients. Pain was assessed using the Visual Analog Pain Scale with a maximum pain rating of 100. Assessments were done at the time of and 18 hours after discharge. MAIN OUTCOME MEASURE: Postoperative pain 18 and 24 hours after discharge was assessed using a standardized questionnaire in a telephone interview by a registered nurse from the Outpatient Surgical Unit. RESULTS: There was no significant difference in the level of pain experienced by 35 patients who received ketorolac intravenously and 35 who received ibuprofen orally. There was no significant difference between the 2 treatment groups in the amount of pain experienced at discharge and 18 hours after discharge. CONCLUSIONS: Pain relief from ibuprofen, 800 mg, administered orally an hour before laparoscopic hernia repair was not statistically different from that obtained with intravenous ketorolac, 60 mg, administered intraoperatively when comparing the hospital discharge pain score and the mean and highest pain scores 18 hours after discharge. Ibuprofen offers equivalent pain control at a lower cost and reduced potential for adverse drug events compared with intravenous ketorolac in patients having laparoscopic hernia repair. No patient required narcotic supplementation, and pain control was judged satisfactory by all the patients.     

Fiber growth initiation in hair follicles of goats treated with melatonin

Amphotericin B (AmB) is the drug of choice for most systemic fungal infections, but doses are frequently reduced because of nephrotoxicity. We investigated the role of thromboxane as a mediator for this nephrotoxicity. Vehicle or amphotericin (0.60 mg/kg) was infused into the left renal artery in four groups of rats, and renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured. Group 1 received vehicle for 90 min. Group 2 received vehicle followed by a 30 minute AmB infusion which caused a significant and reversible fall in the RPF and GFR. Group 3 received vehicle followed by AmB infusion, but were infused with a bolus of ibuprofen (20 mg/kg) 45 minutes before AmB. This group exhibited an insignificant attenuation in the fall in RPF and GFR. Group 4 received vehicle followed by AmB, but were infused with a bolus and continuous infusion of the thromboxane receptor antagonist SQ29,548. This group demonstrated an attenuation in the fall in RPF and a significant decrease in GFR compared to AmB control rats. In addition, the rat glomeruli were incubated with AmB (4 ug/ml). Supernatant levels of thromboxane B2 were significantly elevated in the presence of AmB vs buffer alone. We conclude that the reduction in RPF and GFR observed with AmB infusion in the rat is partially mediated by release of thromboxane.     

Phosphatidylcholine-associated aspirin accelerates healing of gastric ulcers in rats

In this double-blind study, we administered lumbar epidural bupivacaine or bupivacaine plus verapamil to investigate the possible role of the calcium channel blocker, verapamil, in postoperative pain. One hundred patients (ASA physical class I or II) scheduled for lower abdominal surgery were randomly assigned to one of four groups. Group 1 received 10 mL of 0.5% epidural bupivacaine injected 15 min before incision, followed by 10 mL of epidural normal saline 30 min after incision. Group 2 received 10 mL of epidural normal saline injected before incision, followed by 10 mL of 0.5% epidural bupivacaine 30 min after incision. Group 3 received 10 mL of 0.5% epidural bupivacaine plus 5 mg of verapamil injected before incision, followed by 10 mL of epidural normal saline 30 min after incision. Group 4 received the same drugs as Group 3, in the reverse order. Pain and mood numeric rating scores, sedation scores, Prince Henry scores, patient-controlled cumulative postoperative analgesic consumption, and the incidence of side effects were assessed 2, 6, 12, 24, and 48 h after the operation in each group. Cumulative postoperative analgesic consumption in Groups 3 and 4 was significantly lower (P < 0.05) than that in Groups 1 and 2 24 and 48 h after surgery. There were no differences in the pain, mood, and sedation scores and the incidence of side effects among the four groups. We conclude that epidural verapamil decreases postoperative pain, possibly by interfering with normal sensory processing and by preventing the establishment of central sensitization. Implications: Calcium plays an important role in pain physiology at the spinal cord level. We examined the effect of bupivacaine plus verapamil (calcium channel blocker) and of bupivacaine alone. We demonstrated that the combination, administered epidurally, resulted in less postoperative analgesic consumption than bupivacaine alone.     

Abdominal wound tumor recurrence after open and laparoscopic-assisted splenectomy in a murine model

PURPOSE: The cause of abdominal wall tumor recurrences after laparoscopic surgery for cancer remains unknown. A recent study from our laboratory using a murine splenic tumor model suggests that poor surgical technique (i.e., crushing of the tumor) and not the CO2 pneumoperitoneum is responsible for port wound tumors. However, in that experiment no actual laparoscopic procedure or manipulation was performed. The purpose of the current study was to determine the rate of abdominal wound tumors after laparoscopic-assisted splenectomy performed via a CO2 pneumoperitoneum vs. open splenectomy using the mouse splenic tumor model. METHODS: To establish splenic tumors, female BALB/c mice (N=72) were given subcapsular splenic injections of a 0.1-ml suspension containing 10(5) C-26 colon adenocarcinoma cells via a left flank incision at the initial procedure. Eight days later, animals were randomized into one of two groups: 1) laparoscopic-assisted splenectomy, or 2) open splenectomy. Laparoscopic-assisted splenectomy animals had three laparoscopic ports placed and then underwent laparoscopic mobilization of the spleen under a CO2 pneumoperitoneum followed by extracorporeal splenectomy via a subcostal incision. Group 2 animals underwent open splenectomy via a subcostal incision after three port incisions were made in the same locations as for laparoscopic-assisted splenectomy mice. The incision was closed after 20 minutes in both groups. Ten days later, the mice were killed and inspected for abdominal wall tumor implants. The experiment was performed via two separate trials. RESULTS: When results of the two trials were combined, there was no significant difference in the incidence of animals in each group with at least 1 port tumor (open, 21 percent; laparoscopic-assisted splenectomy, 33 percent; P=0.14). However, the overall incidence of port site tumors (number of ports with tumors/total number of ports for each group) was significantly higher in the laparoscopic-assisted splenectomy group than in the open group (20 vs. 7 percent; P=0.01). The subcostal incisional tumor recurrence rate was also higher in the laparoscopic-assisted splenectomy group (50 vs. 21 percent; P=0.02). as was the perioperative mortality rate (21 vs. 7 percent; P=0.08). Results of the two individual trials were also considered separately. The incidence of port wound tumors decreased significantly from the first to the second laparoscopic-assisted splenectomy trial (36 vs. 9 percent; P=0.003), although the incidence of tumors at the subcostal incision and the mortality rate for the two laparoscopic-assisted splenectomy group trials were not significantly different. The open group tumor incidences did not change from trial to trial. CONCLUSIONS: Overall, significantly more port and incisional tumors were noted in the laparoscopic-assisted group. Although not statistically significant, mortality rate of the laparoscopic-assisted group was higher than the open group. The reasons for these findings are unclear. Laparoscopic mobilization was quite difficult and required excessive splenic manipulation, which may have liberated tumor cells from the primary tumor and facilitated port tumor formation. With increased experience, less manipulation was required to complete mobilization. Of note, the incidence of port tumors in the laparoscopic-assisted splenectomy group decreased significantly from the first to the second trials; therefore, it is possible that surgical technique is a factor in port tumor formation. However, the persistently high tumor incidence at the subcostal incision site argues against the hypothesis that the second trial's laparoscopic mobilizations were less traumatic. The CO2 pneumoperitoneum may also be a factor. Further studies are warranted to clarify these issues.     

Effect of chronically infused adrenomedullin in two-kidney, one-clip hypertensive rats

The hypotensive effect of chronically infused adrenomedullin, a potent vasodilator peptide, was examined in conscious two-kidney, one-clip (2K-1C) hypertensive and sham-operated rats. They were infused with 1.0 microgram/h of synthetic human adrenomedullin for 14 days by means of osmotic minipumps. Control groups were infused on the same schedule with 0.9% saline. Systolic blood pressure was measured before and during the infusion. Plasma renin activity, aldosterone and human adrenomedullin concentrations were determined at day 14 of the infusion. A significant reduction of systolic blood pressure was observed in the adrenomedullin-infused 2K-1C rats at day 4, and systolic blood pressure remained significantly lower throughout the experiment compared to that of the control 2K-1C. A similar hypotensive effect was seen in the adrenomedullin-infused sham-operated rats. Both the plasma renin activity and aldosterone concentrations of the adrenomedullin-infused 2K-1C and sham groups were significantly reduced compared to those of the respective control, whereas, the plasma human adrenomedullin concentration in the adrenomedullin-infused groups was found to be within the physiological range. These findings demonstrated that chronically infused adrenomedullin had a hypotensive effect accompanied by significant reductions of plasma renin activity and plasma aldosterone concentration in 2K-1C hypertensive and sham-operated rats.