The prevention of post-operative adhesions using a gastrointestinal prokinetic agent

Attempts have previously been made to reduce adhesion formation by promoting early intestinal motility. The prokinetic agent Cisapride was used in an animal model of end-to-end large bowel anastomoses. Twenty Wistar rats receiving Cisapride 1 mg/kg subcutaneously (sc) twice daily for two days post-operatively were compared with 20 controls receiving saline 0.2 mL in a similar regimen. The points of adhesion of the anastomosis to the following structures were enumerated: tubal fat; mesentery; omentum; caecum; small bowel; and abdominal wall. The treatment group had significantly fewer adhesions: 2.8 +/- 0.9 v 4.3 +/- 1.0. This was mainly in the number of small bowel attachments, 3.8% compared with 37.8%. The study was repeated using small bowel anastomoses. Cisapride again reduced the number of adhesions compared with controls: 2.1 +/- 0.4 v 4.2 +/- 1.4. Cisapride therapy resulted in greater post-operative stool weights and food consumption: control, 3.87 +/- 1.1 stool, 17.04 +/- 4.3 g food; Cisapride 4.43 +/- 0.9 g stool, 19.8 +/- 4.7 g food. The enhanced motility did not affect the anastomotic strength of the small bowel; bursting pressures at a constant inflation rate of 1.1 mL/min were: control 212.8 +/- 56.0 mmHg; Cisapride, 215.8 +/- 58.9 mmHg (NS).     

Gastric residual volume in children: a study comparing efficiency of erythromycin and metoclopramide as prokinetic agents

Metoclopramide may be used to stimulate gastric emptying whenanaesthetizing children for emergency operations. Unfortunately,metoclopramide is associated with extrapyramidal side effects.Erythromycin, a motilin receptor agonist, is a prokinetic agentbut its use has been little investigated in children. This randomizeddouble-blind study compared the effects of premedication withoral metoclopramide 0.15 mg kg^–1 or erythromycin1 mg kg^–1 on gastric emptying in 80 childrenundergoing tonsillectomy. Pre-operative fluids, premedicationand anaesthetic technique were standardized and gastric volumewas measured with an orogastric tube. Post-operative nauseaand vomiting was recorded. Metoclopramide and erythromycin producedsimilar gastric volumes (0.29 and 0.24 ml kg^–1)and there was no difference in post-operative vomiting. In theerythromycin group there were more patients with negative aspirates(45.9%) than in the metoclopramide group (35.1%), but the differencewas not statistically significant. These results indicate thaterythromycin may be as effective as metoclopramide as a prokineticagent. Br J Anaesth 2001; 86: 869–71     

Midazolam as an induction agent in children: a pharmacokinetic and clinical study

The pharmacokinetics of midazolam was studied in 21 children undergoing elective surgery at five different dose levels for induction of general anesthesia and were compared with a control group (n = 6) given thiopental, 5 mg/kg. The clearance of midazolam was found to be dose-related. The elimination half-life varied from 0.79 to 2.83 hr, which is shorter than in adult patients. Even a dose of 0.6 mg/kg midazolam was found to be unreliable as an agent for induction of anesthesia. Compared with thiopental 5 mg/kg, significantly longer times of onset to closing of the eyes (P less than 0.01) and the disappearance of eyelid reflex (P less than 0.01) were seen with midazolam.     

Hyperthermia as a teratogenic agent

The common cotton-eared marmoset, a nonhuman primate with a narrow zone of thermoneutrality, was used in an experiment to assess the effects of hyperthermia as a teratogenic agent. Mild heat stress conditions were used. The results of this preliminary study justify further investigation of the effect of hyperthermia on the primate embryo during morphogenesis.     

Cold as a therapeutic agent

Summary The use of cold as a therapeutic agent has a long and colorful history. The Edwin Smith Papyrus, the most ancient medical text known, dated 3500 B.C., made numerous references to the use of cold as therapy. Baron de Larrey, a French army surgeon during Napoleon’s Russian campaign, packed the limbs in ice prior to amputations to render the procedures painless. In the early twentieth century, a neurosurgeon, Temple Fay, pioneered “human refrigeration” as a treatment for malignancies and head injuries. In 1961, Irving Cooper developed the first closed cryoprobe system and ushered in the modern era of cryogenic surgery with his imperturbable convictions. Fay’s early work fell victim to the disruptive sequel of the World War II. The Nazis confiscated his data (presented before the Third International Cancer Congress in 1939) forwarded to Belgium for publication and brutally applied his refrigeration techniques experimentally without any benefit of anesthesia in the concentration camps, especially Dachau. Hypothermia became associated in the public mind with the atrocities exposed at the war trials in Nürnberg. After lying dormant for decades, the interest was rekindled in the late 80s when mild hypothermia was shown to confer dramatic neuroprotection in a number of experimental models of brain injury. With several large multi-center clinical studies currently under way, hypothermia is receiving unprecedented attention from the medical and scientific communities.     

Advantages of cyclosporine as sole immunosuppressive agent in children with transplanted kidneys.

A prospective study of intentional stopping of steroids 6 months after transplantation was done with 29 pediatric renal transplant recipients with a mean age of 10.4 +/- 3.4 years. Immunosuppression consisted of cyclosporine and methylprednisolone. We stopped giving MP to 24 children: to twenty after six months, four after 11-20 months. "Crude graft survival" was 97% during a mean follow-up of 36.7 +/- 15 months. The rejection rate was 48% during the first 6 months and 29% in the period after stopping MP. At present, 20/24 children (83%) have remained on CsA alone (18 patients) or CsA and azathioprine (2 patients) during a mean follow-up of 30 +/- 17 months. CsA nephrotoxicity occurred in 20.6% of patients, gum hypertrophy in 45%, hypertrichosis in 24%, and neurological symptoms in two patients (6.8%). Linear growth significantly improved after stopping MP: mean catch-up growth for prepuberal children 1.38 height standard deviation score (HSDS) and for pubertal children 1.6 HSDS. Bone age did not increase more rapidly than chronologic age. Weight/height index (W/HI) also improved. There was also a significant reduction in the use of antihypertensive drugs. Calculated glomerular filtration rate was decreased, though not significantly, after stopping MP. Thus, when graft survival is good, stopping corticosteroids corrects the major handicap of children with irreversible uremia--the poor linear growth--and improves the W/HI and control of arterial pressure. Longer follow-up periods are necessary to exclude significant worsening of renal function and an increased incidence of chronic rejection after stopping the steroid.     

Propofol as an induction agent in children: pain on injection and pharmacokinetics

The efficacy of lignocaine (1%) mixed with propofol in reducing pain on injection with propofol was studied in 40 children undergoing elective surgery in a double-blind, randomized comparison with glucose (5%). The pharmacokinetics of propofol in a single dose of 2.5 mg/kg was also studied in eight children participating in the same study. Lignocaine (1 mg) significantly reduced pain on injection compared to the control group (P less than 0.001). The induction characteristics of propofol were not affected by the lignocaine, and no undesirable interaction was found between the two drugs. The first-stage elimination half-life (t1/2 beta) of propofol in children was shorter (mean 9.3 +/- 3.8 (s.d.) min) than the values found in adults. This pharmacokinetic alteration may have clinical significance following repeated administration or continuous infusion of propofol.     

Labetalol as a hypotensive agent in otological operations.

The usefulness of labetalol, a new combined alpha and beta adrenoceptor antagonist as a hypotensive agent in otological operations was studied in 18 otherwise healthy patients. After a single 1.0 mg/kg i.v. dose the maximum decrease in systolic (18%) and diastolic (8%) blood pressure occured between 5 to 15 minutes (mean 11 min), and the pretreatment blood pressure values were reached in 15 to 55 min (mean 26 min). Similarly, after a single 2.0 mg/kg i.v. dose the maximum blood pressure decrease (32%/20%) was observed in 5 to 40 minutes (mean 23.5 min) lasting 30 to 95 minutes (mean 60.1 min). Generally, a moderate decrease in blood pressure without a concomitant increase in heart rate or excessive hypotension was found.     

Irinotecan as a new agent for urachal cancer

The urachal carcinoma, in a 64-year-old male with multiple lung metastases, had shown the resistance to several anti-neoplastic agents including cisplatinum, methotrexate, 5-FU, doxorubicin, epirubicin, and mitomycin C. Because the tumor was adenocarcinoma producing mucin and serum carcinoembryonic antigen (CEA) increased, which resembled colorectal carcinoma, we administrated Irinotecan, which was very effective as the CEA decreased from 98.3 to 38.7 ng/ml and the pulmonary metastatic lesions were reduced by 60%. To our knowledge, this is the first case with urachal carcinoma in which Irinotecan was effective.     

Indications of chlormethiazole as a protective agent in experimental endotoxemia

Chlormethiazole, which is derived from the thiazole moiety of thiamine, possesses sedative, hypnotic and anticonvulsant properties. This anesthetic agent was compared with ketamine in a porcine model of endotoxemia to evaluate effects on cardiovascular and pulmonary function, oxygen delivery and survival. Continuous 6-hour intravenous infusion of Escherichia coli endotoxin caused pronounced pulmonary and cardiovascular derangement and decreases in oxygen delivery and pH in 13 pigs given ketamine anesthesia. Eight of thirteen pigs survived the observation period. Contrastingly, 10 pigs given chlormethiazole anesthesia and endotoxin showed a significantly attenuated response. Thus, the increases in mean pulmonary arterial pressure, venous admixture and extravascular lung water were significantly lower and the decreases in cardiac output, oxygen delivery and pH were significantly modified by chlormethiazole. All 10 pigs survived the observation period. Chlormethiazole may increase the clearance of endotoxin and thus ameliorate the endotoxin response. Although extrapolating from animal data requires great caution, these data may favor the use of chlormethiazole in septic states requiring surgical intervention and anesthesia and as sedation in critically ill septic patients in our intensive care units.     

Assessment of methotrexate as a potential immunosuppressive agent in baboons

Methotrexate is an anti-proliferative agent that affects both T-cell and B-cell immunity, and therefore might be expected to suppress antibody (Ab) production. Although it has been used in xenotransplantation studies to suppress anti-pig Ab production, it has always been used in combination with other immunosuppressants. The purpose of this study was to measure its effect as a single immunosuppressant on anti-Gal Ab production in baboons (n=4). Pharmacokinetic studies showed that methotrexate was not detected in the blood when administered per os. Prolonged daily IV or IM administration (i) reduced T-cell and B-cell numbers by 50% to 70% and modestly reduced responsiveness on mixed lymphocyte reaction (but only at toxic doses) and (ii) did not result in lowered anti-Gal Ab levels, only marginally reducing the rate of return of Ab after extracorporeal immunoadsorption. Our observations would suggest that methotrexate will not contribute significantly to immunosuppressive regimens in the baboon at non-toxic doses.     

Hyperbaric nitrous oxide as a sole anesthetic agent in humans

Nitrous oxide (N2O) has been used to produce analgesia and anesthesia for more than 100 yr. However, because of its high MAC value (1.04), general anesthesia with N2O can usually be attained only in a hyperbaric environment. Because of the sparsity of documentation for human physiologic responses to hyperbaric N2O, we studied eight male volunteers at 2 ATA (1520 mm Hg) anesthetized with N2O only for periods of 2-4 h. N2O partial pressures ranged from 836 to 1368 mm Hg. The anesthetic state was associated with tachypnea, tachycardia, increases in systemic blood pressure, mydriasis, diaphoresis, and at times, clonus and opisthotonus. A stable level of physiologic activity was difficult to maintain.