Wallace M. Nogami

assessment of Low-flow Sevoflurane and Isoflurane Effects on Renal Function Using Sensitive Markers of Tubular Toxicity

Background: Carbon dioxide absorbents degrade sevoflurane, particularly at low gas flow rates, to fluoromethyl‐2,2‐difluoro‐1‐(trifluoromethyl)vinyl ether (compound A). Compound A causes renal proximal tubular injury in rats but has had no effect on blood urea nitrogen (BUN) or creatinine concentrations in patients. This investigation compared the effects of low‐flow sevoflurane and isoflurane on renal tubular function in surgical patients using conventional (BUN and creatinine) and finer indices of renal injury, specifically those biomarkers sensitive for compound A toxicity in rats (glucosuria, proteinuria, and enzymuria [N‐acetyl‐beta‐D‐glucosaminidase (NAG) and alpha‐glutathione‐S‐transferase (alpha GST)]). Methods: Consenting patients with normal preoperative renal function at two institutions were randomized to receive sevoflurane (n = 36) or isoflurane (n = 37) in oxygen and air. Total gas flow was 1 l/min, opioid doses were minimized, and barium hydroxide lime was used to maximize anesthetic degradation. Inspiratory and expiratory compound A concentrations were quantified every 30–60 min. Blood and urine were obtained before and 24–72 h after anesthesia for laboratory evaluation. Results: Sevoflurane and isoflurane groups were similar with respect to age, weight, sex, American Society of Anesthesiologists status, anesthetic duration (3.7 or 3.9 h), and anesthetic exposure (3.6 or 3 minimum alveolar concentration [MAC]‐hour). Maximum inspired compound A concentration (mean +/‐ standard deviation) was 27 +/‐ 13 ppm (range, 10–67 ppm). Areas under the inspired and expired compound A concentration versus time curves (AUC) were 79 +/‐ 54‐ppm‐h (range, 10–223 ppm‐h) and 53 +/‐ 40 ppm‐h (range, 6–159 ppm‐h), respectively. There was no significant difference between anesthetic groups in postoperative serum creatinine or BUN, or urinary excretion of protein, glucose, NAG, proximal tubular alpha GST, or distal tubular pi GST. There was no significant correlation between compound A exposure (AUC) and protein, glucose, NAG, alpha GST, or pi GST excretion. Postoperative alanine and aspartate aminotransferase concentrations were not different between the anesthetic groups, and there were no significant correlations between compound A exposure and alanine or aspartate aminotransferase concentrations. Conclusions: The renal tubular and hepatic effects of low‐flow sevoflurane and isoflurane were similar as assessed using both conventional measures of hepatic and renal function and more sensitive biochemical markers of renal tubular cell necrosis. Moderate duration low‐flow sevoflurane anesthesia, during which compound A formation occurs, appears to be as safe as low‐flow isoflurane anesthesia.

Postcesarean epidural morphine: a dose-response study.

The purpose of this study was to describe the dose-response relationship of epidural morphine for postcesarean analgesia for quality of analgesia and relation to the side effects of pruritus, nausea, and vomiting. Sixty term parturients undergoing nonurgent cesarean delivery were enrolled and randomized to receive a single dose of epidural morphine after delivery (0,1.25, 2.5, 3.75, or 5 mg). A patient-controlled analgesia (PCA) device provided free access to additional analgesics. PCA morphine use and the incidence and severity of side effects were recorded for 24 h. Data were analyzed with analysis of variance, Student’s t-tests, and &khgr;2 analysis. Nonlinear regression was used to describe a dose-response curve. PCA use differed significantly among groups (P < 0.001); PCA use was significantly greater in Group 0 mg than Groups 2.5, 3.75, and 5 mg (P < 0.05). PCA use was also significantly greater in Group 1.25 mg than Groups 3.75 and 5 mg (P < 0.05). Pruritus scores were significantly higher in all groups given epidural morphine than the control group (0 mg) (P < 0.05), but did not differ among the treatment groups (1.25–5 mg), although pruritus scores were significantly higher in treatment groups than in the control (P < 0.05). No relation was found between epidural morphine dose and incidence or severity of nausea and vomiting. We concluded that, for optimal analgesia, augmentation of epidural morphine with systemic analgesics or other epidural medications may be necessary. Implications: Quality of analgesia increases as the dose of epidural morphine increases to at least 3.75 mg; increasing the dose further to 5 mg did not improve analgesia. Side effects were not dose related. For optimal analgesia, augmentation of epidural morphine with systemic analgesics or other epidural medications may be necessary.

Bacterial/fungal growth in a combined parenteral nutrition solution

Appropriately mixed, compatible solutions of glucose, amino acids and lipid have recently become available for clinical use. While a single hyperalimentation solution has several advantages over the conventional two-bottle technique, its effect on infusion-related septicemia is unknown. An in vitro, mock infusion system identical to that used in our new-born intensive care unit was set up to assess the relative growth rates of three microorganisms in several parenteral nutrition mixtures. Growth of Staphylococcus epidermidis, Escherichia coli and Candida albicans was measured in seven different alimentation solutions, including two combined solutions. Generally, microbial growth was the same or decreased in combined solutions as compared to fat alone although considerably greater than that observed in nonlipid containing solutions. In addition, the ability of these organisms to pass in-line terminal filters of pore size 0.22 and 1.2 microns was assessed.

High Carboxyhemoglobin Concentrations Occur in Swine during Desflurane Anesthesia in the Presence of Partially Dried Carbon Dioxide Absorbents

Background: Increased carboxyhemoglobin concentrations in patients receiving inhalation anesthetics (desflurane, enflurane, and isoflurane) have been reported. Recent in vitro studies suggest that dry carbon dioxide absorbents may allow the production of carbon monoxide. Methods: The authors used high fresh oxygen flow (5 or 10 l/min) through a conventional circle breathing system of an anesthesia machine for 24 or 48 h to produce absorbent drying. Initial studies used 10 l/min oxygen flow with the reservoir bag removed or with the reservoir bag left in place during absorbent drying (this increases resistance to gas flow through the canister). A third investigation evaluated a lower flow rate (5 l/min) for absorbent drying. Water content of the absorbent and temperature were measured. Pigs received a 1.0 (human) minimum alveolar concentration desflurane anesthetic (7.5%) for 240 min using a 1 l/min oxygen flow rate with dried absorbent. Carbon monoxide concentrations in the circuit and carboxyhemoglobin concentrations in the pigs were measured. Results: Pigs anesthetized with desflurane using Baralyme exposed to 48 h of 10 l/min oxygen flow (reservoir bag removed) had extremely high carboxyhemoglobin concentrations (more than 80%). Circuit carbon monoxide concentrations during desflurane anesthesia using absorbents exposed to 10 l/min oxygen flow (reservoir bag, 24 h) reached peak values of 8,800 to 13,600 ppm, depending on the absorbent used. Carboxyhemoglobin concentrations reached peak values of 73% (Baralyme) and 53% (soda lime). The water content of Baralyme decreased from 12.1 +/‐ 0.3% (mean +/‐ SEM) to as low as 1.9 +/‐ 0.4% at the bottom of the lower canister (oxygen flow direction during drying was from bottom to top). Absorbent temperatures in the bottom canister increased to temperatures as high as 50 [degree sign] Celsius. With the reservoir bag in place during drying (10 l/min oxygen flow), water removal from Baralyme was insufficient to produce carbon monoxide (lowest water content = 5.5%). Use of 5 l/min oxygen flow (reservoir bag removed) for 24 h did not reduce water content sufficiently to produce carbon dioxide with desflurane. Conclusions: An oxygen flow rate of 10 l/min for 24 h in a conventional anesthesia circuit can dry carbon dioxide absorbents sufficiently to produce extremely high levels of carbon monoxide with high carboxyhemoglobin concentrations in desflurane‐anesthetized pigs. When the reservoir bag is in place on the anesthesia machine or when a lower oxygen flow rate (5 l/min) is used, carbon dioxide absorbent drying still occurs, but 24–48‐h exposure time is insufficient to allow for carbon monoxide production with desflurane.

A Randomized, Double-masked, Multicenter Comparison of the Safety of Continuous Intrathecal Labor Analgesia Using a 28-Gauge Catheter versus Continuous Epidural Labor Analgesia

Background:Continuous intrathecal labor analgesia produces rapid analgesia or anesthesia and allows substantial flexibility in medication choice. The US Food and Drug Administration, in 1992, removed intrathecal microcatheters (27–32 gauge) from clinical use after reports of neurologic injury in nonobstetric patients. This study examined the safety and efficacy of a 28-gauge intrathecal catheter for labor analgesia in a prospective, randomized, multicenter trial. Methods:Laboring patients were randomly assigned to continuous intrathecal analgesia with a 28-gauge catheter (n = 329) or continuous epidural analgesia with a 20-gauge catheter (n = 100), using bupivacaine and sufentanil. The primary outcome was the incidence of neurologic complications, as determined by masked neurologic examinations at 24 and 48 h postpartum, plus telephone follow-up at 7–10 and 30 days after delivery. The secondary outcomes included adequacy of labor analgesia, maternal satisfaction, and neonatal status. Results:No patient had a permanent neurologic change. The continuous intrathecal analgesia patients had better early analgesia, less motor blockade, more pruritus, and higher maternal satisfaction with pain relief at 24 h postpartum. The intrathecal catheter was significantly more difficult to remove. There were no significant differences between the two groups in neonatal status, post–dural puncture headache, hemodynamic stability, or obstetric outcomes. Conclusions:Providing intrathecal labor analgesia with sufentanil and bupivacaine via a 28-gauge catheter has an incidence of neurologic complication less than 1%, and produces better initial pain relief and higher maternal satisfaction, but is associated with more technical difficulties and catheter failures compared with epidural analgesia.

Bupivacaine augments intrathecal fentanyl for labor analgesia.

BACKGROUND fentanyl has been shown to be an effective analgesic for labor; this study investigated the analgesic effect of low-dose bpivacaine added to intrathecal fentanyl for labor analgesia METHODS Ninety parturients in active labor who requested regional analgesia were randomized to receive an intrathecal injection of either fentanyl, 25 microg; bupivacaine, 1.25 mg, with fentanyl, 25 microg; or bupivacaine, 2.5 mg, with fentanyl, 25 microg, as part of a combined spinal-epidural technique. Visual analog pain scores were recorded before and at intervals after injection until the patient requested further analgesia. Maternal blood pressure and fetal heart rate were recorded before and at intervals after injection. Lower-extremity muscle strength was tested before and 30 min after injection; anesthetic level to cold sensation and the presence and severity of pruritus were recorded. RESULTS Duration of analgesia was longer in the group receiving bupivacaine, 2.5 mg, and fentanyl, 25 microg, than the group receiving plain fentanyl (108 vs. 92 min; P < 0.05). Onset of analgesia was faster in both groups receiving bupivacaine compared with plain fentanyl (P < 0.05). No differences in muscle strength after injection were found in any group, although anesthetic levels to cold were documented in all patients in the bupivacaine groups, and 21 of 30 in the plain fentanyl group. Baseline fetal heart rates did not change after injection in any group, and maternal blood pressure was unchanged. CONCLUSIONS The addition of 2.5 mg isobaric bupivacaine to 25 microg fentanyl for intrathecal labor analgesia modestly increases duration and speeds onset of analgesia compared with plain intrathecal fentanyl.

Synergistic effect of coumadin and cytoxan in reducing lung metastases

Lung metastasis is a frequent cancer complication resulting in significant mortality. This study evaluates the effect of coumadin and cytoxan alone and in combination on lung metastases in rats challenged with Morris hepatoma 3924A. Seventy-seven male American Cancer Institute (ACI) rats weighing 200 g were studied. Thirty-seven rats received coumadin orally for six days, which resulted in a prothrombin time 2 times that of controls (30 sec). All rats received 1 X 10(5) clumped Morris hepatoma cells via tail vein injection. Animals were divided into four groups: Group I (controls, n = 20) received no antitumor treatment; group II rats (n = 20) received 25 mg/kg cytoxan intraperitoneally at the time of tumor challenge; group III animals (n = 19) received coumadin alone; while group IV (n = 18) received both coumadin and cytoxan. Rats were evaluated for number of lung metastases and lung weight at 3 weeks postinjection. Data was subjected to statistical analysis by the Students test. The mean number of lung metastases were 580 +/- 45 in group I, 350 +/- 310 in group II, 330 +/- 263 in group III, and 200 +/- 161 in group IV (P less than .005 [IV] v [I], P less than .05 [IV] v [II], [III]), (P less than .05 [II] v [I]), (P less than .05 [III] v [I]). Mean lung weights were 2.597 g +/- 1.65 in group I, 2.049 g +/- 0.75 in group II, 1.898 g +/- 0.80 in group III, and 1,677 g +/- 0.31 in group IV. (P less than .025 [IV] v [I], P less than .05 [IV] v [II]).(ABSTRACT TRUNCATED AT 250 WORDS)