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Biomedical subjects

R Jhaveri

Publications and source records attributed to R Jhaveri.

At least 19 recordsLinked to original sources

Dose comparison of remifentanil and alfentanil for loss of consciousness.

BACKGROUND: This study evaluated the efficacy and safety of remifentanil, a potent mu agonist opioid with a rapid onset and offset of effect, as a sole induction agent for loss of consciousness (LOC) and compared it with alfentanil. METHODS: Remifentanil and alfentanil were administered intravenously over 2 min in ascending doses (remifentanil 2, 3, 4, 5, 6, 8, 10, 15, 20 microg/kg; alfentanil 40, 60, 80, 100, 120, 160, 200 microg/kg) to unpremedicated healthy patients. Patients were observed for rigidity and LOC for 30 s after the end of infusion. If patients had not lost consciousness, 2 mg x kg(-1) x min(-1) thiopental was administered until LOC was achieved. Arterial blood samples, obtained at specified time intervals, were analyzed for remifentanil and alfentanil whole-blood concentration. Blood pressure and heart rate were also recorded at preset time intervals. RESULTS: Neither drug could reliably produce LOC. With both drugs, there was a dose-dependent decrease in thiopental requirements and a dose-dependent increase in the incidence and severity of rigidity (P < 0.05). The median effective dose (ED50) for LOC with remifentanil was 12 microg/kg, and for alfentanil it was 176 mcrog/kg. The median effective concentration (EC50; whole-blood concentration) of remifentanil was 53.8 ng/ml and for alfentanil it was 1,012 ng/ml. Minimal hemodynamic changes were observed after either drug was given. CONCLUSIONS: Remifentanil is 15 times more potent than alfentanil, based on the ED50 to achieve loss of response to a verbal command and 20 times more potent than alfentanil based on the EC50. Neither opioid is suitable as a sole induction agent.

Adult

Opioid-sparing effects of a low-dose infusion of naloxone in patient-administered morphine sulfate.

BACKGROUND: A naloxone infusion is effective in reducing epidural and intrathecal opioid-related side effects. The use of naloxone infusion concomitant with intravenous morphine patient-controlled analgesia (PCA) has not been evaluated, probably because of an expected direct antagonism of the systemic opioid effect. The authors compared the incidence of morphine-related side effects and the quality of analgesia from two small doses of naloxone infusion. METHODS: Sixty patients classified as American Society of Anesthesiologists physical status 1, 2, or 3 who were scheduled for total abdominal hysterectomies were enrolled in the study. Patients received a standardized general anesthetic. In the postanesthetic care unit, patients received morphine as a PCA. They were randomized to receive either 0.25 microg x kg(-1) x h(-1) naloxone (low dose), 1 microg x kg(-1) x h(-1) (high dose), or saline (placebo) as a continuous infusion. Verbal rating scores for pain, nausea, vomiting, and pruritus; sedation scores; requests for antiemetic; and morphine use were recorded for 24 h. Blood pressure, respiratory rate, and oxyhemoglobin saturation were also monitored. RESULTS: Sixty patients completed the study. Both naloxone doses were equally effective in reducing the incidence of nausea, vomiting, and pruritus compared with placebo (P < 0.05 by the chi-squared test). There was no difference in the verbal rating scores for pain between the groups. The cumulative morphine use was the lowest in the low-dose group (42.3 +/- 24.1 mg; means +/- SD) compared with the placebo (59.1 +/- 27.4 mg) and high-dose groups (64.7 +/- 33.0 mg) at 24 h (P < 0.05 by analysis of variance). There was no incidence of respiratory depression (<8 breaths/min) and no difference in sedation scores, antiemetic use, respiratory rate, and hemodynamic parameters among the groups. CONCLUSIONS: Naloxone is effective in preventing PCA opioid-related side effects. Naloxone infusion at 0.25 microg x kg(-1) x h(-1) not only attenuates these side effects but appears to reduce postoperative (beyond 4-8 h) opioid requirements. This dosing regimen can be prepared with 400 microg naloxone in 1,000 ml crystalloid given in 24 h to a patient weighing 70 kg.

Adult

MAC reduction of isoflurane by sufentanil.

We have shown previously that a plasma fentanyl concentration of 1.67 ng ml-1 reduced the MAC of isoflurane by 50%. By comparing equal degrees of MAC reduction by sufentanil, we may determine the potency ratio of these opioids. Seventy-six patients were allocated randomly to receive predetermined infusions of sufentanil, and end-tidal concentrations of isoflurane in oxygen. Blood samples were obtained 10 min after the start of the infusion, and just before and after skin incision. Any purposeful movement by the patient was recorded. The MAC reduction of isoflurane produced by sufentanil was obtained using a logistic regression model. A sufentanil plasma concentration of 0.145 ng ml-1 (95% confidence limits 0.04, 0.26 ng ml-1) resulted in a 50% reduction in the MAC of isoflurane. At a plasma concentration greater than 0.5 ng ml-1, sufentanil exhibited a ceiling effect.

Adult

The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision.

BACKGROUND: We have previously demonstrated that the minimum alveolar concentration of isoflurane at 1 atm that is required to prevent movement in 50% of patients or animals exposed to a maximal noxious stimulus is markedly reduced by increasing fentanyl concentrations. Total intravenous anesthesia with propofol is increasing in popularity, yet the propofol concentrations required for total intravenous anesthesia or the interaction between propofol and fentanyl have not yet been defined. METHODS: Propofol and fentanyl were administered via computer-assisted continuous infusion to provide pseudo-steady-state concentrations and allow equilibration between plasma-blood concentration and their biophase concentration. For the induction of anesthesia patients were randomly allocated to receive propofol only or propofol plus fentanyl 0.2, 0.8, 1.5, 3.0, and 4.5 ng/ml. In each group patients were randomized to target propofol concentrations of 1.5-10 micrograms/ml. At 7 and 10 min arterial blood samples were taken for subsequent measurement of propofol and fentanyl concentrations. At 10 min loss of consciousness was assessed by the patients' ability to respond to a simple verbal command. Thereafter a new target concentration of propofol was entered to ensure loss of consciousness, and succinylcholine was administered to facilitate tracheal intubation. Patients were rerandomized to a new target concentration of propofol (1-19 micrograms/ml) until skin incision. Before skin incision and 1 min after skin incision, arterial blood samples were again obtained for subsequent measurement of fentanyl and propofol concentrations. At skin incision and for 1 min the patient was observed for purposeful movement. Only samples in which the pre- and poststimulus drug concentrations were within 35% of each other were included. The propofol blood concentration at which 50% or 95% of patients did not respond to verbal command (Cp50s and Cp95s, respectively) and to skin incision (Cp50i and Cp95i, respectively), were calculated by logistic regression. RESULTS: There were 56 evaluable patients for calculating the propofol Cp50s and 53 patients for calculating the propofol Cp50i. For propofol alone the Cp50s was 3.3 micrograms/ml and the Cp95s 5.4 microgram/ml. Increasing fentanyl concentrations reduced the Cp50s (P = 0.03), and increasing age decreased the Cp50s (P = 0.04). For propofol alone the Cp50i was 15.2 (95% confidence interval 7.6-22.8) micrograms/ml and the Cp95i 27.4 micrograms/ml. Increasing fentanyl concentrations markedly reduced the Cp50i (P < 0.01), with a 50% reduction in Cp50i produced by 0.63 ng/ml fentanyl. The propofol Cp50i was decreased by 63% with 1 ng/ml fentanyl and 89% by 3 ng/ml fentanyl. At higher fentanyl concentrations the decrease in Cp50i was proportionally less, demonstrating a ceiling effect. CONCLUSIONS: We defined the propofol concentration required for loss of consciousness and showed that it is reduced by increasing fentanyl concentration and by increasing age. The propofol concentration (alone) adequate for skin incision is high but is markedly reduced by fentanyl. A ceiling effect in the Cp50i for propofol is seen with fentanyl concentrations greater than 3 ng/ml.

Adult

Breast cancer after radiation exposure in childhood.

Reports in the literature link radiation in childhood to some form of breast cancer in later life. The authors present a report on the carcinogenic effects of chemotherapy and radiation on the pubescent breast of a 12-year-old female treated for Wilms' tumor of the left kidney.

Adult

Treatment of upper airway obstruction associated with goiter.

The authors examined the resolution of spirometric indices of upper airway obstruction (UAO) following surgical treatment for goiter. The results of a recent study suggest that the integrity of the upper airway remains intact but prolonged recovery is required.

Adult

Oxidant-mediated lung disease in newborn infants.

High concentrations of oxygen are administered with increased airway pressure to most preterm neonates with respiratory distress syndrome (RDS). Among 20% to 30% of survivors a form of chronic lung disease, bronchopulmonary dysplasia (BPD), develops. Its pathogenesis may include tissue damage caused by the superoxide anion (O2-) and other free oxygen radicals. Animal experiments and other data suggested a rationale for superoxide dismutase (SOD) administration in an effort to prevent or ameliorate BPD. Our preliminary studies in 19 prematures with RDS demonstrated its safety in human newborns and permitted measurement of its plasma levels. No adverse clinical findings occurred, and laboratory parameters were unchanged. Subcutaneous administration (0.25 mg/kg) of bovine SOD led to detectable levels at 1 1/2 h (mean 0.22 microgram/ml), with a slight rise to a higher peak at 2 1/2-4 h and a plateau over the remainder of the 12-h interval. Following doses 2-5, peak levels of 0.64 microgram/ml occurred at 4-8 h. With this background, a prospective double-blind controlled study of 45 neonates (mean gestational age, 29 weeks; birth weight, 1,100 g) showed a statistically significant reduction in prevalence of clinical and X-ray signs of BPD with fewer days of continuous positive airway pressure required. The safety and pharmacokinetics of bovine SOD were confirmed.

Antioxidants

Serial trypsin inhibitory capacity and ceruloplasmin levels in prematures at risk for bronchopulmonary dysplasia.

Oxidant injury and release of proteolytic enzymes in prematures with respiratory distress syndrome (RDS), who are treated with ventilators and oxygen, have been postulated as possible causes of bronchopulmonary dysplasia (BPD). The premature may be at particular risk due to low levels of antiproteases, such as alpha-1-proteinase inhibitor (alpha 1PI), and antioxidants, such as ceruloplasmin (CER). Both alpha 1PI and CER deficiencies have been correlated with the severity of RDS. We studied serial alpha 1PI activity as measured by trypsin inhibitory capacity (TIC) and CER in the serum 27 prematures who required ventilator therapy for RDS. Serum TIC values for day 1 were significantly lower (0.34 vs. 0.92 mg inhibited/ml of sample) in the 13 patients who developed BPD compared to the 14 who did not. No significant differences were seen on succeeding days. No significant differences in CER were seen, although both groups had levels 33-50% of adult normals (11.3 vs 9.3 mg/dl). Other significant variables included birthweight (p less than 0.005), severity of RDS (p less than 0.03), and gestational age (p less than 0.03). One way analysis of variances demonstrated day 1 TIC to be the most significant variable (p less than 0.0001), followed by weight (p less than 0.007), severity RDS (p less than 0.04), and gestational age (p less than 0.03). CER levels were not a significant variable. A formula utilizing unstandardized canonical discriminant function including day 1 TIC, birthweight, severity of RDS, and gestational age was 100% sensitive and 85% specific in the prediction of BPD for the original study group. In an additional 25 consecutive admissions with severe RDS of whom 18 survived, the formula was 100% sensitive (6/6) and 75% specific (9/12).(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight

Phototherapy effect on the incidence of patent ductus arteriosus in premature infants: prevention with chest shielding.

Patent ductus arteriosus is common among premature neonates, especially those with birth weights less than 1,500 g. In vitro, room light inhibits the contraction of immature piglet's ductal rings. Because phototherapy is used frequently from the first days of life to treat jaundice in preterm neonates, we compared the occurrence of patent ductus arteriosus among premature infants exposed to this intense light source with those whose chests were shielded. Seventy-four babies with respiratory distress syndrome were randomly assigned to either a treatment group (chest shielded with aluminum foil while on phototherapy, 36 babies) or control group (no shield, 38 babies). All were on radiant warmers, received mechanical ventilation for respiratory distress syndrome, and phototherapy (Air Shields model PTU 78-1) from day 1 of life. Irradiance was maintained at greater than 4.0 microW/cm2/nm in all cases. Although both groups had similar birth weights, gestational ages, severity of respiratory distress syndrome, intravenous fluid intake, and duration of phototherapy, the incidence of patent ductus arteriosus was significantly less in the shield group (shield 11/36 v No shield 23/38; P = .009). Patent ductus arteriosus murmurs developed in shielded patients at a later date, they required less vigorous treatment (ie, indomethacin), and they had shorter hospitalizations (74 v 85 days; P less than .05). The significant reduction of patent ductus arteriosus with shielding suggests that phototherapy may play a role in the occurrence of patent ductus arteriosus in premature infants. Shielding may be a practical method to decrease this common complication should this initial observation be confirmed.

Ductus Arteriosus, Patent

Prevention of bronchopulmonary dysplasia by administration of bovine superoxide dismutase in preterm infants with respiratory distress syndrome.

The effectiveness of bovine superoxide dismutase (SOD) in the prevention of bronchopulmonary dysplasia was evaluated in a prospective double-blind controlled study in 45 neonates (mean gestational age 28.7 weeks, mean weight 1154 gm) with severe respiratory distress syndrome. All were ventilator dependent with FiO2 greater than or equal to 0.7 at 24 hours of age. Either bovine SOD (0.25 mg/kg) or saline solution was administered subcutaneously every 12 hours according to random selection until patients could be maintained in room air without ventilatory or continuous positive airway pressure (CPAP) support. SOD levels were detected in all patients given treatment. Mean peak values at 4 hours after dose ranged from 0.15 micrograms/ml (dose 1) to 0.45 micrograms/ml (dose 10). The drug was well tolerated, and no side effects were detected. Among the 31 survivors (SOD 14, placebo 17) radiologic evidence of BPD was significantly less in patients given SOD (3/14 vs 12/17, P = 0.008). Clinical signs of bronchopulmonary dysplasia (wheezing, pneumonia) were less in patients given SOD (3/14 vs 11/17, P = 0.019). Patients given SOD required fewer days of CPAP (P less than 0.003). There were no differences in days of O2 therapy, intermittent positive pressure breathing, or incidence and severity of patent ductus arteriosus or intraventricular hemorrhage. This preliminary study suggests that SOD may be helpful in reducing the severity of bronchopulmonary dysplasia in infants with respiratory distress syndrome.

Animals

Partial duplication for the short arm of chromosome 2 : the 2p23 to pter syndrome.

A 32 week, small for gestational age neonate was found to have partial duplication of the short arm of chromosome 2 (2p23 to pter). This duplication was due to a paternal balanced translocation [46,XY,t(2;20)(p23;q13)]. Peculiar facies with prominent eyes, low set ears and anteverted nostrils was apparent. A PDA with congestive heart failure occurred in the first weeks of life. The patient also had a marked diastasis recti, hemivertebrae, long tapering fingers and rocker bottom feet. The propositus was similar to the 14 cases of 2p duplication previously reported. It appears that duplication of the distal end of 2p (2p23 to pter), with or without deletion, should be classified as duplication (2p) syndrome.

Abnormalities, Multiple

Safety and plasma concentrations of bovine superoxide dismutase administered to human premature infants.

The safety and plasma concentrations of bovine superoxide dismutase (SOD), potentially useful in prevention of bronchopulmonary dysplasia, were evaluated in 19 prematures with severe IRDS. All were respirator dependent and required FiO2 greater than 0.7 at 24 h of age. Subcutaneous tests (0.1 mg/kg) and treatment doses (0.25 mg/kg) did not induce wheal and flare or systemic reactions. No abnormalities in serum electrolytes, calcium, glucose, creatinine concentrations, complete blood and platelet counts were noted. Following dose 1, SOD was detectable in all patients at 1 1/2 h and rose slowly to a peak at 4-8 h. Mean levels remained between 0.2 and 0.36 micrograms/ml during the 12-hour interval between doses. Similar responses resulted following doses 2-5 with mean levels between 0.36 and 0.68 micrograms/ml. SOD levels varied directly with serum creatinine levels obtained at the time of SOD administration but other factors such as skin perfusion were not controlled. The present study demonstrates that SOD at a dose of 0.25 mg/kg s.c. can be administered safely to prematures with severe IRDS and resulted in levels associated with therapeutic effects in adults.

Animals

Evaluation of modified gowning procedures in a neonatal intensive care unit.

The effect of modified gowning techniques in a neonatal intensive care unit was evaluated. During alternate two-month intervals, no gowns were worn over street clothes in patient care areas by staff or visitors. Mortality and infections rates during these "modified" gowning intervals were the same as during the gowning periods. However, the incidence of necrotizing enterocolitis was significantly greater in the modified gowning periods (7/353) than in the gowning periods (1/371). An expansion of this one-year study to include another year showed an even greater effect. The prevalence of bacteria at three anatomic sites (nares, umbilicus, and groin) on days 2, 4, 7, 10, 14, 21, and 28 of hospitalization was comparable between those studied during modified gowning and gowning intervals. Exceptions were the significantly increased prevalence of Staphylococcus epidermidis in the groin (days 21 and 28) during gowning and S aureus in the nares (day 28) during modified gowning periods.

Bacterial Infections