IV paracetamol effect on propofol–ketamine consumption in paediatric patients undergoing ESWL

Purpose

Electroshock wave lithotripsy (ESWL) is a painful procedure performed with sedoanalgesia in paediatric patients. The propofol?Cketamine combination may be the preferable anaesthesia for this procedure, and propofol?Cketamine consumption may be decreased with the administration of intravenous (IV) paracetamol. In this study we investigated the effect of IV paracetamol administration on propofol?Cketamine consumption, recovery time and frequency of adverse events in paediatric patients undergoing ESWL.

Methods

Sixty children, ranging in age from 1 to 10?years and with American Society of Anesthesiologists Physical Status 1?C2, were included in this prospective, randomized, double-blinded study. Thirty minutes prior to the procedure children randomly assigned to Group I received IV 15?mg/kg paracetamol, and those randomly assigned to Group II received 1.5?mL/kg IV saline infusion 30?min. The propofol?Cketamine combination was prepared by mixing 25?mg propofol and 25?mg ketamine in a total 10?mL solution in the same syringe. After the administration of 0.1?mg/kg midazolam and 10???g/kg atropine to both groups and during the procedure, the propofol?Cketamine combination was administered at 0.5?mg/kg doses to achieve a Wisconsin sedation score of 1 or 2. Oxygen saturation and heart rate were recorded at 5-min intervals. Propofol?Cketamine consumption, recovery times and adverse events were also recorded.

Results

Demographic data were similar between groups. Propofol?Cketamine consumption (Group I, 25.2?±?17.7?mg; Group II, 35.4?±?20.1?mg; p?=?0.04) and recovery times (Group I, 19.4?±?7.9?min; Group II, 29.6?±?11.4?min; p?Conclusion Our data suggest that the administration of IV paracetamol decreases propofol?Cketamine consumption for adequate sedation during ESWL procedures in paediatric patients and shortens recovery time.     

Does ketamine or magnesium affect posttonsillectomy pain in children?

BACKGROUND: Many previous studies have suggested a role for the N-methyl-D-aspartate (NMDA) receptor antagonists ketamine and magnesium in decreasing postoperative pain and analgesic requirements in adults, but none has investigated these medications in children. METHODS: This randomized, double-blind, placebo-controlled study evaluated the effects of ketamine and magnesium in children undergoing tonsillectomy. Eighty patients, aged 3-12 years, were randomly assigned to four groups. Patients received either ketamine 0.15 mg.kg-1, magnesium sulphate 30 mg.kg-1, ketamine 0.15 mg.kg-1 plus magnesium sulphate 30 mg.kg-1, or placebo intravenously 5 min prior to the start of surgery. Intraoperative analgesia was standardized, and included fentanyl and dexamethasone. RESULTS: There were no differences among the groups with respect to pain assessment postoperatively. Compared with placebo, the treatment groups did not require less fentanyl in the postanaesthesia recovery room or consume less codeine in the first 24-h postoperatively. There was no evidence of synergism between ketamine and magnesium. There were no differences among the groups in the incidence of nausea, vomiting, sedation, bleeding, or dreaming postoperatively. CONCLUSION: This study did not demonstrate a decrease in pain or analgesic consumption in children undergoing tonsillectomy when pretreated with a small dose of ketamine and/or magnesium.     

Revising a dogma: ketamine for patients with neurological injury?

We evaluated reports of randomized clinical trials in the perioperative and intensive care setting concerning ketamine's effects on the brain in patients with, or at risk for, neurological injury. We also reviewed other studies in humans on the drug's effects on the brain, and reports that examined ketamine in experimental brain injury. In the clinical setting, level II evidence indicates that ketamine does not increase intracranial pressure when used under conditions of controlled ventilation, coadministration of a gamma-aminobutyric acid (GABA) receptor agonist, and without nitrous oxide. Ketamine may thus safely be used in neurologically impaired patients. Compared with other anesthetics or sedatives, level II and III evidence indicates that hemodynamic stimulation induced by ketamine may improve cerebral perfusion; this could make the drug a preferred choice in sedative regimes after brain injury. In the laboratory, ketamine has neuroprotective, and S(+)-ketamine additional neuroregenerative effects, even when administered after onset of a cerebral insult. However, improved outcomes were only reported in studies with brief recovery observation intervals. In developing animals, and in certain brain areas of adult rats without cerebral injury, neurotoxic effects were noted after large-dose ketamine. These were prevented by coadministration of GABA receptor agonists. IMPLICATIONS: Ketamine can be used safely in neurologically impaired patients under conditions of controlled ventilation, coadministration of a {gamma}-aminobutyric acid receptor agonist, and avoidance of nitrous oxide. Its beneficial circulatory effects and preclinical data demonstrating neuroprotection merit further animal and patient investigation.     

Is the site of action of ketamine anesthesia the N-methyl-D-aspartate receptor?

Synaptic mechanisms underlying ketamine anesthesia were studied using in vitro preparations of the lamprey CNS. Although lampreys are one of the most primitive vertebrates, the synaptic physiology and pharmacology are similar to those in the higher vertebrates. Axonal conduction, transmitter release from the presynaptic terminal, postsynaptic response to the putative neurotransmitters, and resting and activated membrane properties were studied in the absence and the presence of various concentrations of ketamine. Ketamine markedly reduced N-methyl-D-aspartate (NMDA)-activated responses, such as depolarizations to bath-applied NMDA and bursting rhythm during "fictive locomotion." The 50% block of the responses took place in the presence of 10-20 microM ketamine, whereas those induced by kainate and quisqualate (the other two subclasses of L-glutamate/L-aspartate agonists) were spared at concentrations higher than 600-800 microM. None of the other neuronal events tested were suppressed in the presence of still higher concentrations of ketamine. The results support the hypothesis that ketamine might exert its anesthetic effect by a pharmacologically specific interaction with the NMDA receptor.     

Does ketamine have preemptive effects in women undergoing abdominal hysterectomy procedures?

Ketamine may produce "preemptive" analgesia when administered before surgically induced trauma. Therefore, we hypothesized that pre- versus postincisional administration of ketamine would improve pain control after abdominal hysterectomy procedures. Eighty-nine patients were randomly assigned to one of three treatment groups according to a placebo-controlled, double-blinded protocol: Group 1 (placebo) received saline 0.04 mL/kg IV immediately before and after surgery; Group 2 (preincision), received ketamine 0.4 mg/kg IV before skin incision and saline at the end of the operation; and Group 3 (postincision), received saline before skin incision, and ketamine 0.4 mg/kg IV was given after skin closure. The general anesthetic technique was standardized in all three treatment groups. During the first postoperative hour, Group 3 experienced significantly less pain than Groups 1 and 2, as assessed by using both visual analog and verbal rating scales. There were no significant differences between Groups 1 and 2 with respect to pain scores, postoperative opioid analgesic requirements, and incidence of postoperative nausea and vomiting. We conclude that a single dose of ketamine 0.4 mg/kg IV fails to produce preemptive analgesic effects. Implications: Even though ketamine 0.4 mg/kg IV has short-lasting acute analgesic effects, it failed to produce a preemptive effect when given before abdominal hysterectomy procedures.     

Does ketamine affect intraoperative electrophysiological monitoring in children undergoing selective posterior rhizotomy?

Objective: Direct dorsal rootlet stimulation with intraoperative electrophysiological monitoring is an adjunct to clinical evaluation during selective posterior rhizotomy. The purpose of this study was to evaluate the impact of ketamine on intraoperative electrophysiological monitoring during selective posterior rhizotomy. Specifically, we sought to determine if low dose ketamine given as part of the anesthesia was associated with changes in intraoperative electrophysiological monitoring in patients who underwent selective posterior rhizotomy. Methods: A retrospective cohort study was conducted using anesthetic records and electrophysiological records of 32 children who had intraoperative electrophysiological monitoring during selective posterior rhizotomy under general anesthesia. Administration and dosage of ketamine preceding the stimulation of dorsal roots was determined from the anesthetic record. A pediatric neurologist, blinded to patient, and to ketamine exposure, evaluated different electrophysiological criteria. Results: Eight children received ketamine and 24 did not receive it. The mean average dose of ketamine was 0.18 mg·kg^?1 (sd : 0.04). We did not find any statistically significant difference in intraoperative electrophysiological response between the ketamine and the control groups. However, we noted some trends: Administration of ketamine preceding the stimulation of dorsal roots was associated with a lower maximal threshold (2.7 mA vs 3.5 mA, P = 0.663) and root thresholds compared with children who did not receive ketamine. In addition, the train response following delivery of the suprastimulation tended to last longer with the presence of ketamine. Conclusions: Administration of low dose ketamine preceding the stimulation of dorsal roots during selective posterior rhizotomy might be associated with lower maximal thresholds and a more sustained train response following stimulation. Physicians should be aware of this finding in order to avoid misinterpreting intraoperative electrophysiological monitoring.     

Interaction of ketamine with μ2 opioid receptors in SH-SY5Y human neuroblastoma cells

Purpose. Ketamine is known to interact with opioid receptors. However, because this agent does not produce opioid-like respiratory depression, it might not interact with μ₂ opioid receptors. Therefore, we have studied the interaction of ketamine with μ₂ opioid receptors expressed in SH-SY5Y cells. Methods. SH-SY5Y cells (passage 70–80) were used to obtain ketamine dose-response curves for inhibition of 0.4 nM [³H][d-Ala²,MePhe⁴,Gly(ol)⁵] enkephalin (DAMGO) binding to μ₂ opioid receptors and of forskolin (1 μM)-stimulated cyclic AMP (cAMP) formation. Results. Ketamine displaced [³H]DAMGO binding in SH-SY5Y cells with a K _i of 12.1 μM. However, this concentrations did not inhibit forskolin-stimulated cAMP formation, although at supraclinical concentrations, significant inhibition was observed with an estimated IC₅₀ of 700 μM. Conclusion. The present study indicates that a clinically relevant concentration of ketamine interacts with μ₂ opioid receptors. However, no agonist activity was observed. Received for publication on September 10, 1998; accepted on January 5, 1999     

The destruction of the lower urinary tract by ketamine abuse: a new syndrome?

OBJECTIVE

To report the clinical spectrum seen in young abusers of street‐ketamine (regular recreational abusers of street‐ketamine, for its hallucinogenic effects) in Hong Kong, presenting with significant lower urinary tract symptoms (LUTS) but with no evidence of bacterial infection.

PATIENTS AND METHODS

We retrospectively analysed the clinical presentations, pelvic pain and urgency/frequency scores, video‐urodynamic studies, cystoscopy findings, histological features of bladder biopsies and radiological findings of 59 ketamine abusers who were referred to the urology units of Princess Margaret and Tuen Mun Hospital, Hong Kong, from March 2000 to December 2007.

RESULTS

Of the 59 patients, all had moderate to severe LUTS, i.e. frequency, urgency, dysuria, urge incontinence and occasionally painful haematuria. Forty‐two (71%) patients had a cystoscopy that showed various degrees of epithelial inflammation similar to that seen in chronic interstitial cystitis. All of 12 available bladder biopsies had histological features resembling those of interstitial cystitis. Urodynamically, either detrusor overactivity or decreased bladder compliance with or without vesico‐ureteric reflux was detected to some degree in all of 47 patients. Thirty patients (51%) had unilateral or bilateral hydronephrosis on renal ultrasonography, and four (7%) showed features suggestive of papillary necrosis on radiological imaging. Eight patients had a raised serum creatinine level.

CONCLUSION

A syndrome of cystitis and contracted bladder can be associated with street‐ketamine abuse. Secondary renal damage can occur in severe cases which might be irreversible, rendering patients dependent on dialysis. The present data do not establish the precise cause nor the incidence. Street‐ketamine abuse is not only a drug problem, but might be associated with a serious urological condition causing a significant burden to healthcare resources.     

Which anesthetic agent alters the hemodynamic status during pediatric catheterization? Comparison of propofol versus ketamine

OBJECTIVE: To compare the effects of propofol and ketamine on systemic and pulmonary circulations in pediatric patients scheduled for elective cardiac catheterization. DESIGN: Prospective, randomized, and blinded. SETTING: University hospital. PARTICIPANTS: Children (n = 41) undergoing cardiac catheterization. INTERVENTIONS: All children were premedicated with oral midazolam 60 minutes before the procedure. Patients were separated into 3 groups according to shunts diagnosed by transthoracic echocardiography before the catheterization procedure: patients without cardiac shunt (Group I, n = 11), left-to-right shunt (Group II, n = 12), and right-to-left shunt (Group III, n = 18). A continuous infusion of propofol (100-200 microg/kg/min) or ketamine (50-75 microg/kg/min) was randomly started in all groups to obtain immobility during the procedure. Hemodynamic data, including systemic venous, pulmonary artery and vein, aortic saturations and pressures, were recorded; Qp/Qs were calculated. The same set of data was recorded before discontinuation of infusions at the end of the procedure. MEASUREMENTS AND MAIN RESULTS: After the propofol administration, in all 3 patient groups propofol infusion was associated with significant decreases in systemic mean arterial pressure. In groups with cardiac shunts (Group II and III), propofol infusion significantly decreased systemic vascular resistance and increased systemic blood flow, whereas pulmonary vascular resistance and pulmonary blood flow did not change significantly. These changes resulted in decreased left-to-right shunting and increased right-to-left shunting; the pulmonary-to-systemic flow ratio decreased significantly. On the other hand, after ketamine infusion, systemic mean arterial pressure increased significantly in all patient groups, but pulmonary mean arterial pressure, systemic vascular resistance, and pulmonary vascular resistance were unchanged. CONCLUSION: In children with cardiac shunting, the principal hemodynamic effect of propofol is a decrease in systemic vascular resistance. In children with intracardiac shunting, this results in an increase in right-to-left shunting and a decrease in the ratio of pulmonary to systemic blood flow, which may lead to arterial desaturation. Ketamine did not produce these changes. The authors suggested that during cardiac catheterization in children, both the anesthesiologists and cardiologists need to know that anesthetic agents can significantly alter the hemodynamic status in children with complex congenital heart defects and affect the results of hemodynamic calculations that are important for decision-making and treatment of these patients.