Biomedical subjects

D R Cook

Publications and source records attributed to D R Cook.

At least 37 records · Page 2Linked to original sources

PubMed1996

Spontaneous versus edrophonium-induced recovery from paralysis with mivacurium.

This study compared spontaneous with edrophonium-induced recovery of neuromuscular transmission (NMT) after mivacurium infusion. During nitrous oxide-narcotic-propofol anesthesia, the electromyogram (EMG) of the adductor pollicis (AP) was recorded and the movement of the first toe in response to stimulation of the posterior tibial nerve was noted. Mivacurium infusion was titrated to produce posttetanic count of 1-5 at the toe and absence of NMT at the AP. Thirty children were assigned to three groups on the basis of age. Edrophonium, 1 mg/kg, with atropine 10 micrograms/kg, was given after the mivacurium infusion when NMT of the AP was 1% or 10% of baseline. In the third group, spontaneous recovery was observed. Edrophonium given when NMT was 11% +/- 1% SEM produced the most rapid recovery, 7.5 +/- 0.6 min to a train-of-four (TOF) ratio (T4/T1) of 0.9 and the shortest interval from T4/T1 of 0.4-0.9, when residual block was likely to be underestimated, 4.8 +/- 0.6 min. Edrophonium given when block was greater produced recovery of the T4/T1 to 0.4 in 2.8 +/- 0.7 min, but the time from then to T4/T1 = 0.9 was 7.9 +/- 1.1 min, as long as during spontaneous recovery. Spontaneous recovery to T4/T1 = 0.9 occurred 12.9 +/- 0.7 min after the first measurable AP EMG. There was no significant relationship between duration of infusion, which ranged from 16 to 135 min, and time to appearance of AP EMG after the infusion, which averaged 3.1 +/- 0.5 min. We recommend that administration of edrophonium to induce reversal of mivacurium be delayed until two responses to a TOF stimuli are observed because this will produce the most rapid recovery and decrease the interval in which residual block may be underestimated.

Anesthesia Recovery Period↗

PubMed1996

Importance of the organ-independent elimination of cisatracurium.

Cisatracurium, one of 10 isomers of atracurium, undergoes pH and temperature-dependent Hofmann elimination in plasma and tissues. The clearance of cisatracurium due to Hofmann elimination and organ elimination was estimated by applying a nontraditional two-compartment pharmacokinetic model with elimination occurring from both compartments to plasma cisatracurium concentration-time data from 31 healthy adult surgical patients with normal renal and hepatic function. The elimination rate constant from the central compartment, intercompartmental rate constants, and the volume of the central compartment were obtained from the model fit. The elimination rate constant from the peripheral compartment could not be independently estimated in vivo and was therefore fixed to the rate of degradation of cisatracurium in human plasma (pH 7.4 and 37 degrees C) and held constant in the model. Total body clearance, Hofmann clearance, organ clearance, and the volume of distribution at steady-state were derived from the model parameter estimates. Renal clearance was calculated from cisatracurium urinary excretion data from 12 of the 31 patients. Clearance values (mean +/- SD) were 5.20 +/- 0.86, 4.00 +/- 1.04, 1.20 +/- 0.71, and 0.85 +/- 0.32 mL.min-1.kg-1 for total body clearance, Hofmann clearance, organ clearance, and renal clearance, respectively. Hofmann clearance accounted for 77% of total body clearance. Organ clearance was 23% of total body clearance. Renal clearance, a component of organ clearance, was 16% of total body clearance. The organ-independent nature of the elimination of cisatracurium was characterized by a relationship between steady-state volume of distribution and total body clearance. The half-life is an independent variable and is not dependent on the total body clearance nor the steady-state volume of distribution. Hofmann elimination is the predominant pathway for cisatracurium elimination in humans.

Adult↗

PubMed1996

Plasma inorganic fluoride concentrations after sevoflurane anesthesia in children.

BACKGROUND: Sevoflurane is degraded in vivo in adults yielding plasma concentrations of inorganic fluoride [F-] that, in some patients, approach or exceed the 50- micron theoretical threshold for nephrotoxicity. To determine whether the plasma concentration of inorganic fluoride [F-] after 1-5 MAC x h sevoflurane approaches a similar concentration in children, the following study in 120 children scheduled for elective surgery was undertaken. METHODS: Children were randomly assigned to one of three treatment groups before induction of anesthesia: group 1 received sevoflurane in air/oxygen 30% (n = 40), group 2 received sevoflurane in 70% N2O/30% O2 (n = 40), and group 3 received halothane in 70% N2O/30% O2 (n = 40). Mapleson D or F circuits with fresh gas flows between 3 and 61/min were used Whole blood was collected at induction and termination of anesthesia and at 1, 4, 6, 12, and 18 or 24 h postoperatively for determination of the [F-]. Plasma urea and creatinine concentrations were determined at induction of anesthesia and 18 or 24 h postoperatively. RESULTS: The mean (+/- SD) duration of sevoflurane anesthesia, 2.7 +/- 1.6 MAC x h (range 1.1-8.9 MAC x h), was similar to that of halothane, 2.5 +/- 1.1 MAC x h. The peak [F-] after sevoflurane was recorded at 1 h after termination of the anesthetic in all but three children (whose peak values were recorded between 4 and 6 h postanesthesia). The mean peak [F-] after sevoflurane was 15.8 +/- 4.6 microns. The [F-] decreased to <6.2 microns b 24 h postanesthesia. Both the peak [F-] (r2 = 0.50) and the area under the plasma concentration of inorganic fluoride-time curve (r2 = 0.57) increased in parallel with the MAC x h of sevoflurane. The peak [F-] after halothane, 2.0 +/- 1.2 microns, was significantly less than that after sevoflurane (P<0.00012) and did not correlate with the duration of halothane anesthesia (MAC x h; r2 = 0.007). Plasma urea concentrations decreased 24 h after surgery compared with preoperative values for both anesthetics (P<0.01), whereas plasma creatinine concentrations did not change significantly with either anesthetic. CONCLUSIONS: It was concluded that, during the 24 h after 2.7 +/- 1.6 MAC x h sevoflurane, the peak recorded [F-] is low (15.8 microns), F- is eliminated rapidly, and children are unlikely to be at risk of nephrotoxicity from high [F-].

Anesthetics, Inhalation↗

PubMed1996

Nitric oxide mediates hepatic cytochrome P450 dysfunction induced by endotoxin.

BACKGROUND: Animals subjected to immunostimulatory conditions (sepsis) exhibit decreased total cytochrome P450 content and decreased P450-dependent drug metabolism. Cytochrome P450 function is of clinical significance because it mediates the metabolism of some opioid and hypnotic drugs. The authors tested the hypothesis that reduced P450 function and decreased drug metabolism in sepsis are mediated by endotoxin-enhanced synthesis of nitric oxide. METHODS: Hepatic microsomes were prepared from male Sprague-Dawley rats in nontreated rats, rats pretreated with phenobarbital and rats receiving aminoguanidine or NG-L-monomethyl-arginine alone. Nitric oxide synthesis was augmented for 12 h with a single injection of bacterial lipopolysaccharides. Nitric oxide synthase was inhibited with aminoguanidine or N(G)-L-monomethyl-arginine during the 12 h of endotoxemia in some animals. Plasma nitrite and nitrate concentrations were measured in vivo, and total microsomal P450 content, and metabolism of ethylmorphine and midazolam in vitro. RESULTS: Administration of endotoxin increased plasma nitrite and nitrate concentrations, decreased total cytochrome P450 content, and decreased metabolism of ethylmorphine and midazolam. Inhibition of nitric oxide formation by aminoguanidine or N(G)-L-monomethyl-arginine partially prevented the endotoxin-induced effects in the nontreated and phenobarbital-treated groups. Aminoguanidine or N(G)-L-monomethyl-arginine alone did not have an effect on either total cytochrome P450 content or P450-dependent drug metabolism. Plasma nitrite and nitrate concentrations correlated significantly negatively with P450 content (nontreated r = -0.88, phenobarbital r = -0.91), concentrations of formed formaldehyde (nontreated r = -0.87, phenobarbital r = -0.95), and concentrations of midazolam metabolites (4-OH midazolam nontreated r = -0.88, phenobarbital r = -0.93, and 1'-OH midazolam nontreated r = -0.88, phenobarbital r = -0.97). CONCLUSIONS: Altered hepatic microsomal ethylmorphine and midazolam metabolism during sepsis is mediated in large part by nitric oxide.

Animals↗

PubMed1996

Testosterone up-regulates androgen receptors and decreases differentiation of porcine myogenic satellite cells in vitro.

Accumulation of DNA is essential for muscle growth, yet mechanisms of androgen-induced DNA accretion in skeletal muscle are unclear. The purpose of this study was to determine whether androgen receptors (AR) are present in cultured skeletal muscle satellite cells and myotubes and examine the effects of testosterone on satellite cell proliferation and differentiation. Immunoblot analysis using polyclonal AR antibodies (PG-21) revealed an immunoreactive AR protein of approximately 107 kDa in porcine satellite cells and myotubes. Immunocytochemical AR staining was confined to the nuclei of satellite cells, myotubes, and muscle-derived fibroblasts. Administration of 10(-7) M testosterone to satellite cells, myotubes, and muscle-derived fibroblasts increased immunoreactive AR. In satellite cells and myotubes, AR increased incrementally after 6, 12, and 24 h of exposure to testosterone. Testosterone (10(-10) - 10(-6) M), alone or in combination with insulin-like growth factor I, basic fibroblast growth factor, or platelet-derived growth factor-BB, had no effect (P > 0.01) on porcine satellite cell proliferation, and testosterone pretreatment for 24 h did not alter the subsequent responsiveness of cells to these growth factors. Satellite cell differentiation was depressed (20-30%) on days 2-4 of treatment with 10(-7) M testosterone. This effect was not reversible within 48 h after treatment withdrawal and replacement with control medium. These data indicate that satellite cells are direct targets for androgen action, and testosterone administration increases immunoreactive AR protein and reduces differentiation of porcine satellite cells in vitro.

Animals↗

PubMed1995

HIV-regulated diphtheria toxin A chain gene confers long-term protection against HIV type 1 infection in the human promonocytic cell line U937.

Gene therapy approaches have recently been investigated for the treatment of acquired immunodeficiency syndrome (AIDS), both in preclinical and clinical studies, because more traditional antiviral agents have proven to be of limited effectiveness. We have previously shown that long-term protection against both laboratory and clinical isolates of human immunodeficiency virus type 1 (HIV-1) was conferred by HIV-regulated diphtheria toxin A (DT-A) chain in a human T cell line. Because the monocyte/macrophage cell is an important reservoir for HIV-1 in infected individuals, we sought here to determine whether HIV-regulated DT-A would also be effective in the promonocytic cell line U937. We report here that long-term protection, conferred by HIV-regulated DT-A, was observed in U937 cells, but that protection was dependent on the stock of HIV IIIB used for challenge. HIV production was measured by p24 assays, polymerase chain reaction (PCR) for HIV vif, gag, and reverse transcriptase (RT) sequences, and cocultivation with peripheral blood mononuclear cells (PBMCs). Complete protection was seen in DT-A-transduced cells with a stock of IIIB propagated on H9 cells and titered on peripheral blood mononuclear cells (PBMCs), while protection in these same cells with a second stock of IIIB, propagated and titered on H9 cells, was only partial and dose dependent.

CD4 Antigens↗

PubMed1995

Cross-reactivity of human Toxoplasma-specific T cells: implications for development of a potential immunotherapeutic or vaccine.

Previous reports from this laboratory have demonstrated that human CD4+ Toxoplasma-specific cytotoxic T cell (CTL) clones generated by stimulation of peripheral blood mononuclear cells with Toxoplasma RH strain antigens also recognized target cells expressing C strain antigens. To extend these observations, additional Toxoplasma isolates were studied. A simple system for assessment of cytotoxicity using T cell lines rather than cloned CTL was used. Stimulation of human peripheral blood mononuclear cells with Toxoplasma RH strain antigens elicited cytotoxic T cell lines specific for target cells expressing antigens derived from many other Toxoplasma strains. Cell lines produced by stimulation with antigens derived from the related, nonpathogenic coccidian Besnoitia jellesoni were also cytotoxic for target cells expressing Toxoplasma antigens. Proliferative responses to many Toxoplasma isolates and to the Toxoplasma p30 protein were also noted.

Animals↗

PubMed1995

Clinical characteristics of sevoflurane in children. A comparison with halothane.

BACKGROUND: For pediatric patients, sevoflurane may be an alternative to halothane, the anesthetic agent used most commonly for inhalational induction. The induction, maintenance, and emergence characteristics were studied in 120 unpremedicated children 1-12 yr of age randomly assigned to receive one of three anesthesia regimens: sevoflurane with oxygen (group S), sevoflurane with nitrous oxide and oxygen (group SN), or halothane with nitrous oxide and oxygen (group HN). METHODS: Anesthetic was administered (via a Mapleson D, F or Bain circuit) beginning with face mask application in incremental doses to deliver maximum inspired concentrations of 4.5% halothane or 7% sevoflurane. End-tidal concentrations of anesthetic agents and vocal cord position were noted at the time of intubation. Elapsed time intervals from face mask application to loss of the eyelash reflex, intubation, surgical incision, and discontinuation of the anesthetic were measured. Heart rate, systolic, diastolic, and mean blood pressures, and end-tidal anesthetic concentrations were measured at fixed intervals. Anesthetic MAC-hour durations were calculated. The end-tidal concentration of anesthetic was adjusted to 1 MAC (0.9% halothane, 2.5% sevoflurane) for at least the last 10 min of surgery. Intervals from discontinuation of anesthetic to hip flexion or bucking, extubation, administration of first postoperative analgesic, and attaining discharge criteria from recovery room were measured. Venous blood was sampled at anesthetic induction, at the end of anesthesia, and 1, 4, 6, 12, and 18-24 h after discontinuation of the anesthetic for determination of plasma inorganic fluoride content. RESULTS: Induction of anesthesia was satisfactory in groups SN and HN. Induction in group S was associated with a significantly greater incidence of excitement (35%) than in the other groups (5%), resulting in a longer time to intubation. The end-tidal minimum alveolar concentration multiple of potent inhalational anesthetic at the time of intubation was significantly greater in patients receiving halothane than in patients receiving sevoflurane. Induction time, vocal cord position at intubation, time to incision, duration of anesthesia, and MAC-hour duration were similar in the three groups. During emergence, the time to hip flexion was similar among the three groups, whereas the time to extubation, time to first analgesic, and time to attaining discharge criteria were significantly greater in group HN than in groups S and SN. Mean heart rate and systolic blood pressure decreased during induction in group HN but not in groups S and SN. The maximum serum fluoride concentration among all patients was 28 microM. CONCLUSIONS: Sevoflurane with nitrous oxide provides satisfactory anesthetic induction and intubating conditions; however, induction using sevoflurane without nitrous oxide is associated with a high incidence of patient excitement and prolonged time to intubation. There were greater decreases in heart rate and systolic blood pressure during induction with halothane than with sevoflurane; however, these differences may be dose-related. The more rapid emergence with sevoflurane when compared with halothane is consistent with the low solubility of sevoflurane in blood and tissues. Children receiving sevoflurane for up to 9.6 MAC-hours did not develop high serum fluoride concentrations.

Anesthesia, Inhalation↗

PubMed1995

Comparison of the neuromuscular effects of mivacurium and suxamethonium in infants and children.

We compared both the time course of neuromuscular blockade and the cardiovascular side-effects of suxamethonium and mivacurium during halothane and nitrous oxide anaesthesia in infants 2-12 months and children 1-12 years of age. Equipotent doses of mivacurium and suxamethonium were studied; 2.2 x ED95 was used in four groups of infants and children, while 3.4 x ED95 was used in two groups of children. Onset of neuromuscular block in infants was not significantly faster with suxamethonium than with mivacurium (P = 0.2). In all infants given suxamethonium, intubating conditions were excellent, while, in 6/10 infants given mivacurium, intubating conditions were excellent. Onset of complete neuromuscular block in children was significantly faster with suxamethonium, 0.9 min compared with mivacurium, 1.4 min (P < or = 0.05). Increasing the dose of suxamethonium or mivacurium in children to 3.4 x ED95 did not change the onset of neuromuscular block. Recovery of neuromuscular transmission to 25% of initial twitch height (T25) in infants and children was significantly faster after suxamethonium than after mivacurium, at 2.5 and 6 min, respectively (P < or = 0.05). In children given 3.4 x ED95 of suxamethonium or mivacurium, recovery from neuromuscular block was almost identical with the dose of 2.2 x ED95, with spontaneous recovery to T25 prolonged by only 0.5 min. No infant or child had hypotension after the mivacurium bolus dose.

Anesthesia Recovery Period↗

PubMed1994

Efficient foreign gene expression in Epstein-Barr virus-transformed human B-cells.

Epstein-Barr virus (EBV) is a herpesvirus that transforms B-cells (B-LCL) and has undergone intense scrutiny owing to its association with Burkitt's lymphoma, nasopharyngeal carcinoma, and immunoblastic lymphomas. B-LCL have also proven useful in the study of human immunology. We describe a novel system for inducing efficient foreign gene expression in B-LCL using biotinylated adenovirus as an endosome-disrupting agent. Plasmid DNA is coupled to the exterior of viral particles by streptavidin-polylysine chimeric proteins. Up to 67% of B-LCL may be induced to express foreign genes in vitro in transient expression systems, and gene expression lasts for at least 17 days. We have expressed firefly luciferase, beta-galactosidase (beta-gal), chloramphenicol acetyltransferase, HIV gag, and env genes, as well as infectious HIV, and the EBV-specific BZLF gene in B-LCL with this system. In vivo delivery of a beta-gal reporter gene to B-LCL was documented in a SCID mouse model. Potential applications include study of genetic regulation of EBV infection and transformation events, study of potential gene therapies for EBV-related B-cell tumors, and production of antigen-presenting cells for use in immunologic assays. Because of the high percentage of cells transformed and the length of foreign gene expression, the possibility of examining foreign gene expression in transient assays, without selection for clonal populations, exists.

Animals↗

PubMed1994

Protein profiles of Brucella suis and Brucella abortus in isoelectric focusing and sodium dodecyl sulphate-polyacrylamide gel electrophoresis.

The protein profiles of five field isolates of Brucella suis and four field isolates of B. abortus were examined. Isoelectric focusing of soluble proteins from cell sonicates produced 28 bands common to both species, with a further 10 bands being unique to a species. No intraspecies variation was detected. Sodium dodecyl sulfate extracted proteins were resolved by polyacrylamide gel electrophoresis. The proteins were transferred to nitrocellulose and then stained. These techniques allowed the demonstration of 35 bands which were common to both species, with a further 15 bands which were unique to one of the two species. Again, no intraspecies variation was detected.

Animals↗

PubMed1994

Gene therapy for B-cell lymphoma in a SCID mouse model using an immunoglobulin-regulated diphtheria toxin gene delivered by a novel adenovirus-polylysine conjugate.

Despite advances in conventional therapy, many lives continue to be lost to common forms of B-cell cancers, including leukemias, lymphomas and multiple myeloma. We propose a novel approach to therapy of such cancers using controlled expression of a diphtheria toxin gene (DT-A) to kill malignant cells. We have previously demonstrated selective killing of various cell types, in vitro and in vivo, by cell-specific, transcriptionally controlled expression of this gene. Organ-specific ablation in otherwise healthy transgenic mice has convincingly demonstrated the exquisite specificity achievable by this technique. In the studies now described, DT-A was delivered in vitro and in vivo using a novel gene delivery system employing DNA physically attached to the exterior of adenovirus. After demonstrating the efficacy of gene delivery to Epstein-Barr virus transformed human B-cells in vitro, in vivo work was performed using a SCID mouse model for B-cell lymphoma, in which protection against tumor was observed. The concepts of tissue-regulated toxin gene therapy, and this novel adenovirus gene delivery system are discussed.

Adenoviridae↗

PubMed1993

Transforming growth factor-beta, basic fibroblast growth factor, and platelet-derived growth factor-BB interact to affect proliferation of clonally derived porcine satellite cells.

Transforming growth factor beta-1 (TGF-beta) stimulated porcine satellite cell proliferation in basal serum-free medium by 25%, but inhibited growth in serum-containing medium by 58%. The effect of TGF-beta on cell proliferation in serum-free medium was examined in combination with the following human recombinant growth factors: platelet-derived growth factor-BB (PDGF), basic fibroblast growth factor (FGF), insulin-like growth factor I (IGF-I), and epidermal growth factor (EGF). TGF-beta inhibited PDGF-stimulated proliferation, enhanced FGF-stimulated proliferation, and had no effect on proliferation stimulated by IGF-I. The response of satellite cells to EGF and TGF-beta in serum-free medium was not different than TGF-beta alone. TGF-beta depressed proliferation stimulated by the following combinations of two growth factors: PDGF and IGF-I, PDGF and EGF, PDGF and FGF, and IGF-I and EGF. In combination with IGF-I and FGF, TGF-beta did not affect proliferation. TGF-beta inhibited proliferation stimulated by the combination of PDGF, EGF, and IGF-I, but had no effect on proliferation stimulated by combinations of three growth factors that included FGF. FGF stimulated proliferation in Minimum Essential Medium containing 10% porcine serum (MEM-10% PS) by 13% above control. When the combination of TGF-beta and FGF was added to MEM-10% PS, a 78% increase in proliferation was observed. Polyclonal antihuman PDGF-AB (this form neutralizes PDGF-AA, AB, and BB) reduced proliferation in MEM-10% PS by 44%. The combination of TGF-beta and anti-PDGF-AB reduced proliferation by 59%, indicating the effects were not additive. These data indicate that: (1) FGF and TGF-beta interact to increase proliferation of clonally derived porcine satellite cells, and (2) the inhibitory effect of TGF-beta on proliferation of clonally derived porcine satellite cells can be primarily attributed to a reduction in the mitogenic effects of PDGF.

Animals↗

PubMed1993

Fibroblast growth factor, epidermal growth factor, insulin-like growth factors, and platelet-derived growth factor-BB stimulate proliferation of clonally derived porcine myogenic satellite cells.

Clonally derived cultures of porcine skeletal muscle satellite cells were developed. The mitogenic effects of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factors (IGF-I and -II), and platelet-derived growth factors (PDGF-AA and -BB) were examined. Individually, bFGF, IGFs, and PDGF-BB stimulated proliferation of porcine satellite cells grown in basal serum-free medium or Minimum Essential Medium containing 2% fetal bovine serum (MEM-2% FBS). EGF stimulated proliferation in MEM-2% FBS, but neither EGF nor PDGF-AA were mitogenic when added to serum-free medium. The interactions among bFGF, EGF, IGF-I, and PDGF-BB were examined in serum-free medium, using growth factor concentrations shown in dose-response experiments to induce maximal proliferative responses (10 ng/ml bFGF, EGF and PDGF-BB, and 50 ng/ml IGF-I). The combination of bFGF and IGF-I dramatically increased proliferation, and IGF-I also synergized with EGF to increase proliferation. EGF, IGF-I, and bFGF interacted with PDGF-BB to stimulate proliferation. With the exception of EGF and bFGF, combinations of two growth factors typically resulted in greater than additive responses. Simultaneous exposure of satellite cells to bFGF, PDGF-BB, EGF, and IGF-I produced a fivefold increase in DNA compared to cells grown in basal serum-free medium. Elimination of EGF did not reduce the mitogenic response, yet removal of IGF-I, bFGF, or PDGF-BB reduced proliferation by approximately 40, 20, and 10%, respectively. These mitogens are likely physiological regulators of porcine satellite cell activity.

Animals↗

PubMed1993

Long-term inhibition of clinical and laboratory human immunodeficiency virus strains in human T-cell lines containing an HIV-regulated diphtheria toxin A chain gene.

The human immunodeficiency virus (HIV) causes persistent infection of T cells. Chemotherapy for infection in humans may slow HIV-related disease progression, but it does not eradicate virus. Thus, other treatment modalities are warranted. We have previously demonstrated that the human T cell line H9, ordinarily permissive for HIV infection, may be protected against infection with the LAI strain of HIV by intracellular immunization with the gene encoding diphtheria toxin A chain (DT-A) under the control of HIV Tat and Rev. Cloned cells were protected for up to 6 days in vitro. We now report protection against the LAI laboratory isolate for up to 59 days, and against clinical HIV strains of differing phenotypic properties and cell tropisms for up to 59 days. In some cases, protection was complete in that no residual HIV was detected by HIV p24 antigen production, co-culture with parental H9 cells, or the polymerase chain reaction (PCR). CD4+ surface expression of DT-A transduced cloned H9 cells was similar to parental H9 in most cases. These results suggest that toxin gene therapy for HIV infection may ultimately be feasible.

CD4 Antigens↗

PubMed1993

Clinical pharmacology of mivacurium in pediatric patients less than off years old during nitrous oxide-halothane anesthesia.

We determined the dose-response relationship of mivacurium in infants 2-6 and 7-11 mo of age during nitrous oxide-halothane anesthesia. The neuromuscular and cardiovascular effects of a bolus dose of mivacurium larger than the ED95 in infants and young children from 2-23 mo of age were observed. The infusion rate of mivacurium required to maintain approximately 95% neuromuscular block was determined. There was no significant difference between the estimated dose-response relationship in infants 2-6 mo and that in infants 7-11 mo. The ED50 and ED95 were 44 micrograms/kg and 85 micrograms/kg for infants 2-11 mo (n = 70), r = 0.53. A bolus dose of 150 micrograms/kg mivacurium in infants (2-6 mo) produced 100% depression of the initial twitch height (T1) in 8 out of 9 infants and 85% depression in 1 infant. The time to onset of maximum block was 1.6 +/- 0.3 (0.7-2.7) (mean, SEM [range]) min, and time to recovery to 25% of T1 (T25) was 7.5 +/- 0.7 (5.5-11) min after 150 micrograms/kg in these patients. A bolus dose of 200 micrograms/kg mivacurium in infants and young children (7-23 mo) produced 100% depression of T1 in 14 of 17 patients, 97% depression in 2, and 90% depression in 1. The time to onset of maximum block was 1.5 +/- 0.1 (0.8-3) min and T25 was 10.3 +/- 1.5 (4.8-30.5) min after 200 micrograms/kg in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗

PubMed1992

Validity of a disposable end-tidal CO2 detector in verifying endotracheal tube placement in infants and children.

STUDY OBJECTIVE: To examine the validity of a disposable, colorimetric end-tidal CO2 detector in verifying endotracheal tube (ETT) placement in infants and children. DESIGN: The detector was studied prospectively in 151 intubations. SETTING: Operating room, ICU, and emergency department of a children's hospital. PARTICIPANTS: One hundred thirty-seven children undergoing endotracheal intubation for anesthesia (52), respiratory support (76), or CPR (23). INTERVENTIONS: After endotracheal intubation, tube position was verified, the detector was attached, and readings were obtained. MEASUREMENTS AND RESULTS: The detector correctly identified tube position (trachea, 124; esophagus, four) in all 120 patients who were not in cardiac arrest (P less than .01). In the cardiac arrest setting, all six esophageal intubations were correctly identified, but two of the 17 tracheal intubations were incorrectly interpreted as esophageal intubations (P less than .01). CONCLUSION: The detector accurately identifies ETT position in children with spontaneous circulation who weigh more than 2 kg. During CPR, a positive test correctly indicates that the ETT is in the airway, but a negative result (suggesting esophageal placement) requires an alternate means of confirming ETT position.

Adolescent↗

PubMed1992

Pharmacokinetics of mivacurium in normal patients and in those with hepatic or renal failure.

We have determined the pharmacokinetics and duration of action of a bolus dose of mivacurium (0.15 mg kg-1) during isoflurane and nitrous oxide anaesthesia in nine patients with normal renal and liver function, nine patients undergoing cadaveric kidney transplantation and nine patients undergoing cadaveric liver transplantation. Total plasma concentrations of mivacurium were measured for 2.5 h after administration using a high-pressure liquid chromatographic assay. Plasma concentration vs time data for what were presumed to be the two active mivacurium isomers were analysed by a non-compartmental method based on statistical moments. Neuromuscular block was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The mean time to recovery of 25% neuromuscular transmission, T25, was greater in the patients with liver failure (57.2 min) than in control patients (18.7 min). The volume of distribution at steady rate (Vdss) was comparable in the three groups. Patients with impaired liver function had significantly longer mean residence time and smaller plasma clearance than did patients with renal failure or control patients. There were significant negative correlations between plasma cholinesterase activity and both T25 (r = 0.79) and mean residence time (r = 0.62).

Adult↗