Safety and efficacy of chloral hydrate sedation in children undergoing echocardiography

The purpose of this prospective study was to determine the safety and efficacy of chloral hydrate sedation in children with known or suspected congenital heart disease. The study population included 405 children with a median age of 13 months (3 weeks to 14 years). Cyanotic heart disease was present in 64 of the children. The median dosage of chloral hydrate given was 77 mg/kg, with a range of 25 to 125 mg/kg. Sedation was achieved in 397 (98%) of the children. The complete study time averaged 2.2 hours (range, 1.6 to 5.2 hours). The time to achieve sedation was 30 minutes or less in 82%, more than 30 but less than 60 minutes in 12%, and more than 60 minutes in 4%; 2% failed to achieve sedation. Children aged 3 years or younger were more likely to be successfully sedated with chloral hydrate (p = 0.003). The type of heart disease did not affect the success of sedation. No child had a clinically significant change in heart rate or blood pressure during sedation; however, oxygen saturation decreased in 24 (6%) of 397 children successfully sedated. Decreases in oxygen saturation occurred more commonly in children with trisomy 21 (7/13) than in children without genetic syndromes (17/384). Vomiting occurred in 23 (6%) of the 405 study subjects, usually immediately after drug administration. Chloral hydrate is a safe and effective agent for sedation of children with known or suspected congenital heart disease who are undergoing echocardiography in the outpatient cardiology clinic.     

Sedation with oral hydroxyzine and rectal chloral hydrate in pediatric MRI and CT

AIM: To assess the efficacy and risks of oral hydroxyzine and rectal chloral hydrate to sedate children undergoing CT or MRI. PATIENTS AND METHODS: 110 children underwent 117 studies. Medical history, treatments, doses per kg of sedative drugs, study quality, sedation time and side effects were prospectively recorded. RESULTS: 25 minutes was the mean time necessary to put children to sleep, 59 minutes was the mean time of sedation 96% of studies were interpretable. 2 children showed transient side effects. CONCLUSION: This sedation regimen appeared efficient. However, its limitations and risks have to be known by radiologists. Sedation-related problems also have to be considered by hospital managers when a new CT or MR equipment is being acquired.     

Stress technetium-99m tetrofosmin myocardial scintigraphy: a new one-hour protocol for the detection of coronary artery disease

The primary objective of this study was to evaluate in a random double-blind design, the sedative and behavioural responses of children undergoing outpatient paediatric dental procedures receiving either chloral hydrate (CH) alone or in combination with hydroxyzine. Forty American Society of Anaesthesiologists class I children (21 to 36 months of age) were randomly allocated to receive either 70 mg/kg CH alone or with 2 mg/kg hydroxyzine. The degree of crying, movement and overall behaviour was evaluated during treatment at different times. The combination of chloral hydrate/hydroxyzine (CH/H) significantly decreased crying and movement in relation to the effect induced by CH alone (p < 0.05) only at 45-60 min following the insertion of a rubber dam, whereas the overall behavior in both groups was no different throughout the dental procedures. In conclusion, our study demonstrated that hydroxyzine increased the effect of CH. However, because of the presence of high rates of oxygen desaturations and of deep sedation, careful use of this drug combination should be stressed.     

Relation between impedance and electrode temperature during radiofrequency catheter ablation of accessory pathways and atrioventricular nodal reentrant tachycardia

OBJECTIVES: To evaluate and compare the clinical efficacy, impact on hemodynamics, safety profiles, and cost of combined administration of propofol and midazolam (synergistic sedation) vs. midazolam and propofol administered as sole agents, for sedation of mechanically ventilated patients after coronary artery bypass grafting. DESIGN: Prospective, controlled, randomized, double-blind clinical trial. SETTING: Intensive care unit of SCIAS-Hospital de Barcelona. PATIENTS: Seventy-five mechanically ventilated patients who underwent coronary artery bypass graft surgery under low-dose opioid anesthesia. INTERVENTIONS: According to the double-blind method, patients were randomly assigned to receive propofol (n = 25), midazolam (n = 25), or propofol combined with midazolam (n = 25). Infusion rates were adjusted to stay between 8 and 11 points on Glasgow Coma Score modified by Cook and Palma. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD duration of sedation was 14.4 +/- 1.5 hrs, 14.1 +/- 1.1 hrs, and 14.7 +/- 1.9 hrs for the propofol, midazolam, and synergistic groups, respectively. The induction dose was 0.55 +/- 0.05 mg/kg for propofol as sole agent, 0.05 +/- 0.01 mg/kg for midazolam as sole agent, and 0.22 +/- 0.03 mg/kg for propofol administered in combination with 0.02 +/- 0.00 mg/kg of midazolam (p = .001). The maintenance dose was 1.20 +/- 0.03 mg/kg/hr for propofol as sole agent, 0.08 +/- 0.01 mg/kg/hr for midazolam as sole agent, and 0.50 +/- 0.09 mg/kg/hr for propofol administered in combination with 0.03 +/- 0.01 mg/kg/hr of midazolam (p < .001). All sedative regimens achieved similar efficacy in percentage of hours of adequate sedation (93% for propofol, 88% for midazolam, and 90% for the synergistic group, respectively). After induction, both propofol and midazolam groups had significant decreases in systolic blood pressure, diastolic blood pressure, left atrial pressure, and heart rate. Patients in the synergistic group had significant bradycardia throughout the study, without impairment in other hemodynamic parameters. Patients sedated with propofol or synergistic regimen awoke sooner and could be extubated before those patients sedated with midazolam (0.9 +/- 0.3 hrs and 1.2 +/- 0.6 hrs vs. 2.3 +/- 0.8 hrs, respectively, p = .01). Synergistic sedation produced cost savings of 28% with respect to midazolam and 68% with respect to propofol. CONCLUSIONS: In the study conditions, the new synergistic treatment with propofol and midazolam administered together is an effective and safe alternative for sedation, with some advantages over the conventional regimen with propofol or midazolam administered as sole agents, such as absence of hemodynamic impairment, >68% reduction in maintenance dose, and lower pharmaceutical cost.     

Fine structure of the spermatozoa of Crassostrea gigas (Mollusca, Bivalvia)

STUDY OBJECTIVES: To compare the effectiveness of intramuscular meperidine (2 mg/kg) and promethazine (1 mg/kg) with chlorpromazine (MPC) or without chlorpromazine (MP) (1 mg/kg) for sedation of children undergoing emergency department procedures. DESIGN: Randomized, double-blind trial. SETTING: A community and university hospital ED. TYPE OF PARTICIPANTS: Eighty-seven hemodynamically and neurologically stable children less than 16 years old. INTERVENTIONS: IM sedation followed by intended procedure. MEASUREMENTS AND MAIN RESULTS: Children receiving either combination were not significantly different with regard to age, sex, weight, chronic illness, and indications. Procedures included laceration repair (46), fracture reduction (25), and others (16). Mean onset of action was similar (16 +/- 12 minutes), whereas the duration of action was significantly longer after MPC (63 +/- 57 minutes [mean +/- SD] compared with MP 29 +/- 36 minutes; P < .05, Student's t-test). Paradoxical hyperactivity occurred only after MP (three of 43 cases; P = NS, Fisher's exact test), whereas transient oxygen desaturation occurred only after MPC (one of 44 cases; P = NS). No other serious complications were observed. Three observers rated the effectiveness of sedation and analgesia on separate 10.2-cm visual-analog scales. Overall, MPC received significantly better ratings (7.4 +/- 2.1 cm) than MP (5.7 +/- 3.0 cm; P < .05, Mann-Whitney U test). Parents believed sedation worked well in 90% of cases. Their children had bad memories of the procedure in only 9% of cases. CONCLUSION: Elimination of chlorpromazine from the IM combination of meperidine and promethazine for pediatric sedation during ED procedures results in a significant reduction in efficacy.     

The effect of sleep on conscious sedation

This study evaluated the effect of preoperative sleep on the success of conscious sedation. Thirty healthy children between the ages of 18 and 61 months of age were utilized in this study. The children all received chloral hydrate (50-60 mg/kg) and hydroxyzine (15-25 mg) and nitrous oxide (30-50%). Parents were asked to complete a questionnaire which asked several questions about their child's activity the previous day, their diet, and questions that related to their bedtime. The operator ranked the sedations on a scale from 1 to 4 with 1 being good and 4 being poor. The results were then statistically evaluated using the non-parametric Mann-Whitney and Kruskal-Walls tests. The children that received a normal amount of sleep or greater amount of sleep preoperatively had a borderline (P = .06) higher degree of successful sedation. There was no correlation between the child's bedtime (early, normal, late) and the success of sedation. The parent's perception of their child's tiredness could not be correlated with the success of the sedation. The children greater than 36 months of age had a significantly (P = .02) higher degree of successful sedations. The results suggest that a well rested child may experience a more pleasant dental sedation while under chloral hydrate and hydroxyzine conscious sedation and that the child's age at the time of the sedation may affect the outcome of the sedation.     

Metformin inhibits ganglionic neurotransmission in renal nerves

Intravenous administration of the antihyperglycemic agent metformin decreases arterial pressure and sympathetic nerve activity (SNA). To test the hypothesis that metformin inhibits SNA by interrupting ganglionic neurotransmission, we compared the actions of intravenous administration of metformin and the ganglionic blocker trimethaphan on postganglionic renal and preganglionic adrenal sympathetic nerves in pentobarbital-anesthetized male Sprague-Dawley rats. Intravenous metformin elicited dose-dependent decreases in postganglionic renal SNA (1 mg/kg: 0 +/- 0%; 10 mg/kg: -20 +/- 4%; 100 mg/kg: -92 +/- 3%; n = 7). Conversely, only the maximal dose of metformin affected preganglionic adrenal SNA (100 mg/kg: delta adrenal SNA = -14 +/- 6%; n = 8). Ganglionic blockade with intravenous trimethaphan (5 mg/kg) produced a differential sympathoinhibitory response similar to the response observed after high-dose metformin (delta renal SNA = -100 +/- 3%; delta adrenal SNA = -17 +/- 7%; P < .001). Preganglionic renal neurons were electrically stimulated in the spinal cord, before and during the peak of the sympathoinhibitory response to intravenous metformin, and the magnitude of the stimulus-evoked increases in postganglionic renal SNA were compared. Metformin dose-dependently attenuated the magnitude of the increase in postganglionic renal SNA elicited by stimulation of the spinal cord (30 mg/kg: -23 +/- 8%; 90 mg/kg: -65 +/- 11%; 270 mg/kg: -91 +/- 8%; n = 6 per dose). We conclude that high-dose intravenous metformin interrupts ganglionic neurotransmission in renal nerves.     

A single dose of morphine sulfate increases the incidence of vomiting after outpatient inguinal surgery in children

BACKGROUND: In children, opioids are valuable both for their analgesic properties and for their salutary effect on emergence delirium. Although intraoperative administration of opioids is often cited as the cause of postoperative emesis, few data quantitating the magnitude of this effect exist. METHODS: Patients undergoing inguinal surgery as outpatients were randomly assigned to one of two groups. One group received a single intravenous dose of morphine 0.1 mg/kg (morphine group), and the other (control) group had the identical anesthetic but instead received saline. Intravenous ketorolac was administered in response to verbal complaints of pain or a Children's Hospital of Eastern Ontario Pain Score greater than 9 on two successive evaluations performed at 5-min intervals. The authors compared the incidence of postoperative emesis and emergence, behavior, and pain scores between the two groups. RESULTS: Patients in the morphine group (n = 48) were 5.6 +/- 2.8 yr old and weighed 20.8 +/- 7.8 kg, and those in the control group (n = 49) were 4.5 +/- 2.9 yr old and weighed 18.9 +/- 9.2 kg. More patients in the morphine group were cooperative and deeply asleep both on arrival and through the first 30 min of their stay in the postanesthesia care unit (PACU) (P < 0.05). Sixty-three percent of the children in the control group received ketorolac in the PACU compared with 20% of the morphine group (P < 0.01). The incidence of emesis for the 24 h after arrival in the PACU was 56% for those who received morphine compared with 25% in the control group (P < 0.01). CONCLUSIONS: For children undergoing inguinal surgery, the administration of a single dose of intravenous morphine after the induction of anesthesia smooths emergence from anesthesia as assessed by improved cooperation and sedation in the PACU, decreases the need for postoperative analgesics, but increases the incidence of vomiting in the first 24 h after surgery.     

Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies

The association of propofol with excitatory motor activity, such as myoclonic jerking and opisthotonus, in humans and in animals suggests that it may aggravate clinical seizure activity in some circumstances, although evidence suggests that under other circumstances, propofol inhibits seizure activity. In the current study, we assessed the effect of sedating doses of propofol on lidocaine-induced seizure activity in spontaneously breathing rats receiving no other anesthetics. Adult Sprague-Dawley male rats, 300-400 g, were divided into a control group and three experimental groups representing three graded levels of propofol sedation. The control rats then received a lidocaine infusion at the rate of 150 mg x kg(-1) x h(-1), resulting in a slow, progressive increase in systemic lidocaine concentrations. At the onset of electroencephalographic (EEG) seizure activity, arterial lidocaine concentrations were obtained. The treated rats received propofol according to three different dose schedules: Dose 1 = 10 mg x kg(-1) x h(-1) after a 2.5-mg/kg bolus; Dose 2 = 20 mg x kg(-1) x h(-1) after a 5-mg/kg bolus; Dose 3 = 40 mg x kg(-1) x h(-1) after a 10-mg/kg bolus. After 30 min, a steady level of sedation, dependent on the dose of propofol, was achieved. The lidocaine infusion was then started, and systemic lidocaine levels were obtained at the onset of EEG seizure activity. The lidocaine was continued until the onset of death by cardiac arrest. Plasma lidocaine was measured by gas chromatography. Analysis of variance and Dunnett's t-test were used for comparisons with the control values. Continuous propofol sedation increased the seizure dose of lidocaine from 37.7 +/- 3.5 mg/kg (mean +/- SEM) to 52.5 +/- 2.6 mg/kg (Dose 1, P < 0.05) and 67.9 +/- 8.6 mg/kg (Dose 2, P < 0.05), and completely abolished lidocaine seizures at Dose 3. The lethal dose of lidocaine, 89.4 +/- 10.5 mg/kg control versus 108.7 +/- 10.3 mg/kg (Dose 1), 98.3 +/- 10.1 mg/kg (Dose 2), and 93.5 +/- 10.4 mg/kg (Dose 3) did not differ among groups. The lidocaine levels at seizure threshold were increased in the propofol-treated rats: 16.9 +/- 0.5 microg/mL control versus 19.2 +/- 0.7 microg/mL (Dose 1, P = not significant) and 23.7 +/- 1.8 microg/mL (Dose 2, P < 0.05). Continuous propofol sedation in spontaneously breathing rats receiving no other anesthetics exerts a protective effect against lidocaine-induced seizures in a monotonic, dose-dependent fashion. The cardiac arrest dose of lidocaine is unaffected by propofol under these conditions. IMPLICATIONS: The i.v. anesthetic drug propofol, given to rats to produce sedation, was found to suppress seizure activity caused by overdosage of the local anesthetic lidocaine.     

Comparative study of oral clonidine and diazepam as premedicants in children

In a prospective, double-blind, controlled study the efficacy of clonidine was assessed in children, with respect to sedation, intubation response, and recovery. Fifty children, aged 4-12 years, undergoing general anesthesia were studied. Twenty-five children (group I) received oral diazepam) 0.2 mg/kg and another 25 children (group II) received oral clonidine 3 micrograms/kg, 90-120 minutes before induction of anesthesia. The level of sedation, hemodynamic changes to laryngoscopy and intubation, the recovery from anesthesia were noted and compared between the groups. Clonidine 3 micrograms/kg produced sedation comparable to diazepam 0.2 mg/kg (p > 0.1). There was significant (p > 0.01) attenuation of hemodynamic intubation response with clonidine. The recovery with clonidine was not delayed (p < 0.01). Clinically significant hypotension and bradycardia were not observed in any of the patients. We conclude that clonidine 3 micrograms/kg produces sedation comparable to diazepam 0.2 mg/kg and also attenuates the intubation response without increasing the incidence of complications.     

Serum and cerebrospinal fluid pharmacokinetics of intravenous and oral lamivudine in human immunodeficiency virus-infected children

We studied the pharmacokinetics of intravenously and orally administered lamivudine at six dose levels ranging from 0.5 to 10 mg/kg of body weight in 52 children with human immunodeficiency virus infection. A two-compartment model with first-order elimination from the central compartment was simultaneously fitted to the serum drug concentration-time data obtained after intravenous and oral administration. The maximal concentration at the end of the 1-h intravenous infusion and the area under the concentration-time curve after oral and intravenous administration increased proportionally with the dose. The mean clearance of lamivudine (+/- standard deviation) in the children was 0.53 +/- 0.19 liter/kg/h (229 +/- 77 ml/min/m2 of body surface area), and the mean half-lives at the distribution and elimination phases were 0.23 +/- 0.18 and 2.2 +/- 2.1 h, respectively. Clearance was age dependent when normalized to body weight but age independent when normalized to body surface area. Lamivudine was rapidly absorbed after oral administration, and 66% +/- 25% of the oral dose was absorbed. Serum lamivudine concentrations were maintained above 1 microM for >/=8 h of 24 h on the twice daily oral dosing schedule with doses of >/=2 mg/kg. The cerebrospinal fluid drug concentration measured 2 to 4 h after the dose was 12% (range, 0 to 46%) of the simultaneously measured serum drug concentration. A limited-sampling strategy was developed to estimate the area under the concentration-time curve for concentrations in serum at 2 and 6 h.     

Patient-controlled analgesia versus patient-controlled analgesia plus continuous infusion after hip replacement surgery

OBJECTIVE: To compare the efficacy and adverse effect profile of patient-controlled analgesia (PCA) versus PCA plus continuous infusion (PCACI) after hip replacement surgery. DESIGN: Prospective, randomized, open pilot study. SETTING: Large teaching institution. PARTICIPANTS: Thirty-four patients undergoing hip replacement or revision of hip replacement surgery. INTERVENTIONS: Patients were randomized to receive PCA morphine: 1 mg with 6-minute lockout, or PCACI, using the same dose, with a 0.5-1 mg/h continuous infusion. Pain intensity, sedation, narcotic use, injection/attempt ratio (I/A), and adverse effects were assessed. RESULTS: No significant differences in pain intensity were identified. Morphine use was not different between groups: PCA 61.8 +/- 35.0 and PCACI 74.2 +/- 54.9 mg (p =0.394). A trend toward an increased 12-hour I/A ratio was evident in the PCACI group: PCA 0.73 +/- 0.18 and PCACI 0.86 +/- 0.17 (p =0.073). Patient-reported adverse effects, sedation, and inability to sleep secondary to pain occurred similarly. Eight of 18 PCACI patients required discontinuation of either the continuous infusion mode or of PCA therapy entirely secondary to adverse effects. CONCLUSIONS: When compared with PCA therapy, PCACI was not associated with improved pain control and more patients receiving PCACI required discontinuation of therapy secondary to adverse effects.     

Reduced neuromuscular blocking potency of atracurium in patients with purulent intrathoracic diseases

OBJECTIVE: Based on personal observations the neuromuscular blocking potency of atracurium was supposed to be diminished in purulent intrathoracic diseases. This hypothesis was tested in a prospective clinical trial. METHODS: 52 adult patients undergoing general anaesthesia (methohexitone, sufentanil, flunitrazepam, N2O, enflurane) for elective thoracic surgery were investigated. After the intubation dose of 0.6 mg/kg atracurium was applied continuously to maintain a 90% suppression of the evoked compound electromyogram. According to the intraoperatively established diagnosis patients were allocated to three categories: 1) non-malignant tumor as the control group (n = 15), 2) lung cancer (n = 22), 3) purulent intrathoracic process without tumor (n = 15). The groups were compared regarding onset time, DUR 10% and maintenance dose of atracurium. RESULTS: Patients with lung cancer did not differ significantly from the controls regarding efficiency of atracurium. In contrast, patients with a purulent intrathoracic process showed a significantly longer onset time (6.3 +/- 2.5 vs. 2.9 +/- 0.8 min, p < 0.001), and a significantly shorter DUR 10% (23 +/- 6 vs. 36 +/- 10 min, p < 0.001) compared to the control group. Mean infusion rate of atracurium to maintain a 90% suppression of the evoked compound electromyogram was significantly higher in patients with a purulent process compared to the controls (10.5 +/- 3.2 vs. 6.0 +/- 1.2 micrograms/kg.min, p < 0.001). CONCLUSION: Our results support the hypothesis that patients with a purulent intrathoracic disease show a clear reduction in neuromuscular blocking potency of atracurium.     

cAMP analogues downregulate the expression of granulocyte macrophage colony-stimulating factor (GM-CSF) in human bone marrow stromal cells in vitro

STUDY OBJECTIVE: To determine the neuromuscular blocking effect and recovery profile of cisatracurium besylate in children after administration of a bolus dose that was twice the estimated dose required to produce 95% of the maximum effect (2 x ED95; 0.08 mg/kg) followed by an infusion during halothane-nitrous oxide anesthesia. STUDY DESIGN: Open-label study. SETTING: Teaching hospital. PATIENTS: 30 male and female (ASA physical status I and II) patients, 2 to 10 years of age, scheduled for elective surgery of low to moderate risk. INTERVENTIONS: After induction of general anesthesia, patients received cisatracurium 0.08 mg/kg administered over 5 to 10 seconds. For surgical procedures requiring neuromuscular block for at least 60 minutes, a second bolus dose of cisatracurium 0.02 mg/kg was administered after the first response to a train-of-four stimuli (T1) recovered to 25% of baseline. When T1 was 5% of baseline after the second dose, a 3 microg/kg/min infusion of cisatracurium was initiated and titrated to maintain 89% to 99% block for the duration of the surgery. For procedures requiring neuromuscular block of less than 60 minutes, one or more maintenance doses of 0.02 mg/kg cisatracurium were administered when T1 was 25% of baseline after the preceding dose. In 10 patients, recovery was facilitated with edrophonium 1.0 mg/kg administered when T1 was 26% to 48% of the final baseline. MEASUREMENTS AND MAIN RESULTS: Evoked muscular response at the adductor pollicis was measured by electromyography. With 0.08 mg/kg, onset time (mean +/- SEM) was 4.1 +/- 0.4 minutes, and clinically effective duration was 27.3 +/- 0.9 minutes. Mean 5% to 95% and 25% to 75% recovery indices were 28.4 +/- 2. 7 minutes and 11.2 +/- 0.8 minutes, respectively. The mean infusion rate necessary to maintain 89% to 99% T1 suppression for 17 to 145 minutes was 1.7 microg/kg/min. After termination of infusion, the mean 5% to 95% and 25% to 75% recovery indices were similar to those after a single bolus dose, and time to 95% recovery was 30.4 +/- 3.0 minutes. After administration of edrophonium, full recovery (T4:T1 > or = 70%) occurred in 1.5 +/- 0.4 minutes. No clinically significant changes in heart rate or blood pressure were noted during the first 5 minutes after administration of cisatracurium 0.08 mg/kg. CONCLUSIONS: Cisatracurium provided maximal neuromuscular block, cardiovascular stability, and predictable recovery at the doses tested. In view of this finding, cisatracurium should be a useful intermediate-duration neuromuscular blocking drug for children during general anesthesia.     

A prospective, randomized, and controlled study of fluid management in children with severe head injury: lactated Ringer's solution versus hypertonic saline

OBJECTIVES: Resuscitation in severe head injury may be detrimental when given with hypotonic fluids. We evaluated the effects of lactated Ringer's solution (sodium 131 mmol/L, 277 mOsm/L) compared with hypertonic saline (sodium 268 mmol/L, 598 mOsm/L) in severely head-injured children over the first 3 days after injury. DESIGN: An open, randomized, and prospective study. SETTING: A 16-bed pediatric intensive care unit (ICU) (level III) at a university children's hospital. PATIENTS: A total of 35 consecutive children with head injury. INTERVENTIONS: Thirty-two children with Glasgow Coma Scores of <8 were randomly assigned to receive either lactated Ringer's solution (group 1) or hypertonic saline (group 2). Routine care was standardized, and included the following: head positioning at 30 degrees; normothermia (96.8 degrees to 98.6 degrees F [36 degrees to 37 degrees C]); analgesia and sedation with morphine (10 to 30 microg/kg/hr), midazolam (0.2 to 0.3 mg/kg/hr), and phenobarbital; volume-controlled ventilation (PaCO2 of 26.3 to 30 torr [3.5 to 4 kPa]); and optimal oxygenation (PaO2 of 90 to 105 torr [12 to 14 kPa], oxygen saturation of >92%, and hematocrit of >0.30). MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and intracranial pressure (ICP) were monitored continuously and documented hourly and at every intervention. The means of every 4-hr period were calculated and serum sodium concentrations were measured at the same time. An ICP of 15 mm Hg was treated with a predefined sequence of interventions, and complications were documented. There was no difference with respect to age, male/female ratio, or initial Glasgow Coma Score. In both groups, there was an inverse correlation between serum sodium concentration and ICP (group 1: r = -.13, r2 = .02, p < .03; group 2: r = -.29, r2 = .08, p < .001) that disappeared in group 1 and increased in group 2 (group 1: r = -.08, r2 = .01, NS; group 2: r = -.35, r2 =.12, p < .001). Correlation between serum sodium concentration and cerebral perfusion pressure (CPP) became significant in group 2 after 8 hrs of treatment (r = .2, r2 = .04, p = .002). Over time, ICP and CPP did not significantly differ between the groups. However, to keep ICP at <15 mm Hg, group 2 patients required significantly fewer interventions (p < .02). Group 1 patients received less sodium (8.0 +/- 4.5 vs. 11.5 +/- 5.0 mmol/kg/day, p = .05) and more fluid on day 1 (2850 +/- 1480 vs. 2180 +/- 770 mL/m2, p = .05). They also had a higher frequency of acute respiratory distress syndrome (four vs. 0 patients, p = .1) and more than two complications (six vs. 1 patient, p = .09). Group 2 patients had significantly shorter ICU stay times (11.6 +/- 6.1 vs. 8.0 +/- 2.4 days; p = .04) and shorter mechanical ventilation times (9.5 +/- 6.0 vs. 6.9 +/- 2.2 days; p = .1). The survival rate and duration of hospital stay were similar in both groups. CONCLUSIONS: Treatment of severe head injury with hypertonic saline is superior to that treatment with lactated Ringer's solution. An increase in serum sodium concentrations significantly correlates with lower ICP and higher CPP. Children treated with hypertonic saline require fewer interventions, have fewer complications, and stay a shorter time in the ICU.     

Oculoplastic surgery with a contact Nd:YAG laser silica scalpel. A case report

The purpose of this study was to evaluate the efficacy of local immunosuppression with intraportal administration of cyclosporine (CsA) in liver transplantation. Mongrel dogs weighing 12-18kg were used. Orthotopic liver transplantation was performed, and animals were divided to the following groups. Group I (n = 7): no treatment, group II (n = 7): CsA 5mg/kg/day intermittent iv, group III (n = 5): CsA 3mg/kg/day continuous iv and group IV (n = 8): CsA 3mg/kg/day continuous portal infusion. Immunosuppressive treatments were carried out for two weeks postransplant. Median survival time (MST) of group IV was significantly prolonged (MST = 18 days, range 10-85 days; p < 0.025) compared with group I (7 days, range 6-13), group II (10 days, range 7-16) and group III (7 days, range 6-10). Data of blood chemical analyses showed that hepatic dysfunction was significantly diminished in group IV compared with other groups (p < 0.05). Blood concentration of CsA on the 5th day (mean +/- SEM) was significantly lower in group IV (238 +/- 22ng/ml) than in group III (438 +/- 113ng/ml). Histologic findings showed that rejection reaction was effectively suppressed in group IV, although SG2M% (mean +/- SEM) of peripheral mononuclear cells of group IV (10.6 +/- 3.3%) was equal to that of group III (11.3 +/- 1.7%). In conclusion, local immunosuppression could achieve prominent effect in preventing hepatic graft rejection with limited systemic immunosuppression.     

Vancomycin pharmacokinetics in neonates and infants: a retrospective evaluation

OBJECTIVE: To evaluate the frequency with which current loading and maintenance vancomycin dosages achieve target serum concentrations based on pharmacokinetic parameters obtained after the initial dose. Also, to identify the daily vancomycin dosage necessary to achieve target serum concentrations at steady-state and to determine if any relationships exist between vancomycin pharmacokinetic parameters and various patient characteristics. SETTING: Neonatal intensive care unit (NICU) at Georgia Baptist Medical Center. PATIENTS/METHODS: Twenty-three infants with suspected or documented gram-positive infection who received intravenous vancomycin between July 1990 and November 1991 were included in this retrospective analysis. Gestational age range from 23 to 41 weeks and postconceptional age (PCA) at the time of the study ranged from 26 to 46 weeks. Vancomycin therapy was initiated with a loading dose of 15 mg/kg, followed by a maintenance dosage of 20-30 mg/kg/d, which was usually given as 10 mg/kg q8-12h. All vancomycin doses were administered using a syringe pump. Peak and trough serum concentrations were obtained following the first dose. Vancomycin pharmacokinetic parameters were determined using a one-compartment model. Infants receiving indomethacin within two weeks prior to study were analyzed separately (group 2, n = 4). All other infants were included in group 1 (n = 19). RESULTS: For group 1, vancomycin clearance (Cl), volume of distribution (Vd), and half-life were (mean +/- 1 SD) 0.072 +/- 0.032 L/kg/h, 0.52 +/- 0.08 L/kg, and 5.6 +/- 1.6 hours, respectively. For both groups, loading doses provided 1-hour postinfusion peak concentrations of 25-35 mg/L in one of every two infants studied, whereas only three percent of initial maintenance doses were projected to provide desired peak and trough concentrations at steady-state. For group 1, the mean daily dosage necessary to provide target peak (25-35 mg/L) and trough (5-10 mg/L) concentrations at steady-state was larger than that initially prescribed (29.6 +/- 13.1 vs. 22.2 +/- 4.7 mg/kg/d). For group 2, the mean daily dosage required to achieve target peak and trough concentrations at steady-state was smaller than that initially prescribed (14.8 +/- 4.3 vs. 20.0 +/- 0.1 mg/kg/d) and was exactly half of that required for group 1. Excellent correlations were observed between PCA and vancomycin Cl (L/h) (r = 0.92; p < 0.0001), body weight and Vd(L) (r = 0.94; p < 0.0001), body weight and vancomycin Cl (L/h) (r = 0.85; p < 0.0001), PCA and Vd (L) (r = 0.89; p < 0.0001), and body surface area and Vd (L) (r = 0.93; p < 0.0001) for group 1. Moderate correlations were also noted between PCA and Cl relative to body weight (L/kg/h), postnatal age and Cl (L/kg/h), and PCA and vancomycin dosage requirements (mg/kg/d). No linear correlation was observed between any patient characteristic and Vd standardized for body weight. CONCLUSIONS: Our data demonstrate the need for a more accurate method of estimating initial vancomycin dosage requirements in this NICU population. Although some of the relationships revealed in this study could be used to determine vancomycin dosage for infants in the range of approximately 30-36 weeks PCA, we hesitate to suggest this approach presently because of the potential limitations of our study design. Further prospective study is needed to confirm these observations. In addition, further study is necessary to describe the time course of the interaction between vancomycin and indomethacin in infants with successful and unsuccessful closure of their patent ductus arteriosus.     

Inhibition of Salmonella enteritidis by oleuropein in broth and in a model food system

OBJECTIVE: To compare the pharmacokinetics of methylprednisolone in renal transplant recipients on 2 occasions separated by at least 1 month during chronic immunosuppression. DESIGN: A prospective unblinded trial. PATIENTS: Ten renal transplant recipients (aged 25-62 years) evaluated in a public university-affiliated hospital clinic. INTERVENTIONS: All patients received their chronic oral dose of methylprednisolone as a 10-20-minute intravenous infusion during the 2 study periods. MAIN OUTCOME MEASURES: Serum methylprednisolone concentrations were determined by HPLC and were used to generate the pharmacokinetic parameters of the drug. RESULTS: During study 1, which ranged from 1.2 to 24 months posttransplant, the mean +/- SD methylprednisolone dose was 13.2 +/- 6.4 mg. In study 2 (2.5-38.5 mo posttransplant), the mean dose was 10.6 +/- 3 mg. During both study periods, methylprednisolone concentrations exhibited a monoexponential decline. Considerable variability in methylprednisolone clearance was observed between periods in certain patients. Four of the 10 patients demonstrated a reduction in clearance from study 1 to study 2, which ranged from a 28% to a 53% decrease. Two patients exhibited an increase in clearance of 40% and 49%. The mean +/- SD total body clearance in study 1 was 363 +/- 330 mL/min/kg, whereas the mean volume of distribution was 1.18 +/- 0.53 L/kg. The mean elimination rate constant was 0.29 +/- 0.14 h-1, with a mean serum half-life of 2.87 +/- 1.15 h during the first phase. In study 2, the mean methylprednisolone clearance was 261 +/- 150 mL/min/kg (p > 0.05) and the mean volume of distribution was 0.89 +/- 0.31 L/kg (p > 0.05). The mean serum half-life of methylprednisolone was 2.91 +/- 0.60 h (p > 0.05), with the mean elimination rate constant of 0.25 +/- 0.06 h-1 (p > 0.05). CONCLUSIONS: These data demonstrate that intrapatient variability in methylprednisolone clearance exists among certain renal allograft recipients. As a result of the observed variability, patients who are continued on the same dose of methylprednisolone during the posttransplant period of chronic immunosuppression will be subjected to a changing pattern of exogenous glucocorticoid exposure. The impact of these changing patterns requires further prospective evaluation.     

Effects of acute ethanol intoxication on experimental brain injury in the rat: neurobehavioral and phosphorus-31 nuclear magnetic resonance spectroscopy studies

Using the lateral fluid-percussion model of experimental brain injury in the rat, the authors investigated the effect of acute ethanol (EtOH) intoxication on cardiovascular changes, neurological motor deficits, brain bioenergetics, and mortality associated with traumatic brain injury. Two hours after gastric administration of EtOH (low dose in 20 animals, 1.5 g/kg; high dose in 28, 3.0 g/kg) or saline (equal volume), animals were subjected to a fluid-percussion brain injury centered over the left parietal cortex. These injuries were of either moderate (X = 2.2 atm; 10 animals/treatment) or high severity (X = 3.0 atm; 18 animals/saline, 10 animals/low-dose EtOH, and 18 animals/high-dose EtOH). Neurological motor function was evaluated daily over a 1-week period, while a subset of eight animals receiving high-dose EtOH and subjected to brain injury of high severity were monitored for 4 hours using phosphorus-31 nuclear magnetic resonance spectroscopy to determine intracellular pH, free magnesium, and brain cytosolic phosphorylation potential. A significant (p < 0.05) and prolonged (up to 1 hour) hypotension was observed in animals pretreated with either low- or high-dose EtOH. Neither low-dose (blood-EtOH concentration = 110 +/- 40 mg/dl) nor high-dose (blood-EtOH = 340 +/- 70 mg/dl) EtOH had any effect on survival or neurological motor function after moderate brain injury. Following severe brain injury, animals pretreated with high-dose (blood-EtOH concentration = 352 +/- 65 mg/dl) EtOH showed a significantly increased mortality and markedly worsened neurological deficits at 24 hours postinjury. Following injury, free magnesium and cytosolic phosphorylation potential declined in both groups by approximately 50% to 60%, with no significant differences between groups with respect to these variables. In contrast, brain intracellular pH in the EtOH-treated animals was consistently higher than in the control group after injury. These data suggest that prior exposure to EtOH, particularly at high concentrations, may have detrimental effects on neurobehavioral function and survival in the acute period (up to 24 hours) after severe brain injury, and may be associated with posttraumatic cerebral alkalosis.