Epidural and subarachnoid blockade in children.
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Analgesia, Epidural↗
Biomedical subjects
E Doyle
Publications and source records attributed to E Doyle.
Modifying infant stress responses to major surgery: spinal vs extradural vs opioid analgesia.
Twenty-six infants due to undergo major abdominal or thoracic surgery under general anaesthesia were randomized to receive additional analgesia with group A) spinal/epidural analgesia; B) epidural analgesia or C) opioid analgesia with fentanyl. We wished to determine if spinal analgesia followed by epidural analgesia might result in more complete control of cardiovascular or stress responses than the other two treatment groups. Heart rate and blood pressure were recorded at five min intervals throughout surgery. Blood samples were taken for measurement of catecholamines and whole blood sugar on induction, 45 min after skin incision and at the end of surgery. Heart rate rose significantly at the start of surgery in groups B and C but not group A. Systolic blood pressures were higher in group C compared to A and B. The rise in plasma glucose concentrations was significantly different between the groups in the order C > B > A (P < 0.05). A similar trend was seen in the plasma adrenaline and noradrenaline concentrations but this failed to achieve significance due to the limited sample size.
Abdomen↗
Pre-emptive effect of multimodal analgesia in thoracic surgery.
Thirty subjects undergoing posterolateral thoracotomy were allocated randomly to receive one of two analgesic regimens: group Pre received i.v. morphine, i.m. diclofenac and intercostal nerve blocks from T2 to T11, 20 min before operation and placebo injections after operation. Group Post received placebo injections before operation, and i.v. morphine, i.m. diclofenac and intercostal nerve blocks from T2 to T11 at the end of surgery, before discontinuation of anaesthesia. Visual analogue pain scores, extent and duration of intercostal nerve block, analgesic consumption and complications were assessed during the postoperative period by a single blinded observer. Subjects were followed-up for a minimum of 12 months to determine the incidence of post-thoracotomy pain syndrome. During the first 48 h after operation there were lower pain scores in group Pre when taking a vital capacity breath but there were no significant differences between the groups in any other measure. The effects of pre-emptive analgesia given before surgery appeared to be relatively modest in terms of analgesia, analgesic consumption and long-term outcome and were of limited clinical significance.
Adult↗
O-glucuronidation, a newly identified metabolic pathway for topotecan and N-desmethyl topotecan.
During topotecan analysis of clinical urine samples, an additional peak eluting just after the solvent front was observed. This potential metabolite was isolated by chromatographic methods. Mass spectrometry data along with chromatographic retention data and fluorescence characteristics showed that the isolated fractions contained two compounds, i.e. topotecan-O-glucuronide and N-desmethyl topotecan-O-glucuronide. The concentrations of the metabolites in human urine were relatively low. When topotecan was given as a 30 min infusion at a dosage of 1.5 mg/m2 daily for five consecutive days every 3 weeks, the maximal metabolite concentrations in a 24 h urine sample were approximately 10% of topotecan-O-glucuronide and 3.5% of N-desmethyl topotecan-O-glucuronide with respect to the concentration of topotecan in the urine. This is the first report demonstrating that glucuronide metabolites of topotecan are present in the urine of treated patients.
Antineoplastic Agents↗
Plasma bupivacaine levels after fascia iliaca compartment block with and without adrenaline.
Twenty children undergoing unilateral surgery on the thigh received a fascia iliaca compartment block using 2 mg.kg-1 of bupivacaine with (Group A) or without (Group P) adrenaline 1/200,000. Venous blood samples were taken as 5, 10, 15, 20, 25, 30, 40, 50 and 60 min after injection and assayed for concentrations of bupivacaine. In all subjects an adequate block was produced. Plasma concentrations of bupivacaine in Group P were significantly higher than those in Group A (P < 0.05). The median maximum plasma concentration (Cmax) was 1.1 micrograms.ml-1 (range 0.54-1.29 micrograms.ml-1) in Group P and 0.35 microgram.ml-1 (range 0.17-0.96 microgram.ml-1) in Group A. The median time taken to attain Cmax (Tmax) was 20 min (range 10-25 min) in Group P and 45 min (range 5-50 min) in Group A. The median time to first analgesia was 9.75 h (range 3-15 h) in Group P and 10.5 h (range 2.5-21 h) in Group A. The study confirmed the efficacy of the fascia iliaca compartment block in children and showed that when performed with 2 mg.kg-1 of bupivacaine it is associated with plasma concentrations of bupivacaine well within acceptable limits. The addition of adrenaline 1/200,000 to the local anaesthetic solution reduces the maximum plasma concentration reached.
Adolescent↗
Congenital heart disease in adults.
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Adult↗
Comparison of caudal block using bupivacaine and ketamine with ilioinguinal nerve block for orchidopexy in children.
Forty boys weighing less than 25 kg undergoing unilateral orchidopexy were randomly allocated to receive one of two analgesic regimens. Group C received a caudal epidural block with 0.25% bupivacaine 1 ml.kg-1 and preservative-free ketamine 0.5 mg.kg-1; Group L received an ilioinguinal nerve block with 0.25% bupivacaine 0.5 ml.kg-1 and infiltration of the wound with 0.25% bupivacaine 0.5 ml.kg-1. All subjects received diclofenac sodium 1-2 mg.kg-1 as a rectal suppository. Postoperative pain was assessed by means of a modified Objective Pain Score and analgesia was administered if this exceeded a value of 4. The median duration of analgesia was 10 h (range 2.6 to > 24 h) in Group C and 2.9 h (range 0.7 to > 24 h) in Group L (p < 0.05). There were no differences between groups in the incidence of motor block, urinary retention, postoperative vomiting or postoperative sedation. Subjects in Group L required significantly more doses of postoperative analgesia than those in Group C (p < 0.05).
Acetaminophen↗
A risk-benefit assessment of topical percutaneous local anaesthetics in children.
Since its introduction, eutectic lidocaine-prilocaine cream ('EMLA')1 has been found to be an effective topical anaesthetic agent, with a high degree of efficacy, particularly for venepuncture and venous cannulation, and an impressive tolerability profile. Reports of adverse effects are remarkable for their rarity. The only problems that are likely to be encountered are oral ingestion of the cream (which may lead to anaesthesia of the oropharynx and possible toxicity secondary to rapid absorption of local anaesthetic from oral mucous membranes) and methaemoglobinaemia following repeated applications in neonates and infants. Analysis of the risks and benefits associated with its use comes down heavily in favour of the preparation. More recently, a preparation of tetracaine (amethocaine) has been marketed as a gel. Its advantages are a faster onset, and longer duration, of action than 'EMLA'. Although less widely used, it too has an impressive tolerability record. Concerns over the potential for anaphylactic type reactions due to its ester structure have not been realised in clinical practice. Of the other available preparations, lidocaine (lignocaine), applied iontophoretically, is unlikely to become popular because of the complexity of administration. A paste made of tetracaine, epinephrine (adrenaline) and cocaine (TAC) appears to be a far more toxic preparation on theoretical grounds, and this has been borne out in clinical practice; it is not as well tolerated as 'EMLA' or tetracaine gel. Ethyl chloride, although not a local anaesthetic, can safely provide cutaneous analgesia in children in circumstances when it is impractical to wait for a local anaesthetic preparation to take effect.
Administration, Cutaneous↗
Nefiracetam (DM-9384) reverses apomorphine-induced amnesia of a passive avoidance response: delayed emergence of the memory retention effects.
Nefiracetam is a novel pyrrolidone derivative which attenuates scopolamine-induced learning and post-training consolidation deficits. Given that apomorphine inhibits passive avoidance retention when given during training or in a defined 10-12h post-training period, we evaluated the ability of nefiracetam to attenuate amnesia induced by dopaminergic agonism. A step-down passive avoidance paradigm was employed and nefiracetam (3 mg/kg) and apomorphine (0.5 mg/kg) were given alone or in combination during training and at the 10-12h post-training period of consolidation. Co-administration of nefiracetam and apomorphine during training or 10h thereafter produced no significant anti-amnesic effect. However, administration of nefiracetam during training completely reversed the amnesia induced by apomorphine at the 10h post-training time and the converse was also true. These effects were not mediated by a dopaminergic mechanism as nefiracetam, at millimolar concentrations, failed to displace either [3H]SCH 23390 or [3H]spiperone binding from D1 or D2 dopamine receptor subtypes, respectively. It is suggested that nefiracetam augments molecular processes in the early stages of events which ultimately lead to consolidation of memory.
Animals↗
The single and multiple dose pharmacokinetics of pranlukast in healthy volunteers.
OBJECTIVE: The pharmacokinetics of pranlukast, a leukotriene LTD4 antagonist, were studied in 48 young, healthy subjects after single and repeated oral doses (given every 12 h) ranging from 112.5 to 675 mg. The doses were administered 30 minutes after a light breakfast. RESULTS: Maximal drug concentrations generally occurred between 2 and 6 h after dosing, and there was some evidence of an absorption lag-time. Secondary peaks were observed in the plasma concentration vs. time profiles of many of the study subjects after both single and repeated doses, particularly during the period of maximum drug absorption. In general, after both single and repeated doses, there were related increases in the corresponding Cmax and AUC with a rise in dose, although the increase was diminished at doses above 450 mg. With repeated dosing of pranlukast the mean AUC was generally higher (up to 1.6-fold), and the higher plasma concentrations allowed characterisation of a longer mean t 1/2 than after single dose administration. The mean steady-state trough plasma concentrations attained after evening doses were considerably higher (up to 14-fold) than those obtained after the morning dose. CONCLUSION: The data suggested that the pharmacokinetics of pranlukast are influenced by the time of dosing. Based on analysis of urinary 6 beta-hydroxycortisol excretion, there was no evidence that pranlukast modified the metabolic activity of cytochrome P-450 3A isoenzymes.
Adolescent↗
The impact of column temperature in the high performance liquid chromatographic analysis of topotecan in rat and dog plasma.
A sensitive high performance liquid chromatographic (HPLC) assay has been developed and validated for the quantitation of the novel anticancer agent topotecan and topotecan as its lactone plus carboxylate forms in rat and dog plasma. Linear responses in analyte standard peak areas were observed over the concentration ranges 0.10-10 ng ml-1 using 100 microliters of rat plasma and 0.2-100 ng ml-1 using 100 microliters of dog plasma. Due to the instability of the drug in the biological matrix it was necessary to obtain the plasma fraction within 5 min after blood sampling by centrifugation, immediately followed by protein precipitation with cold methanol (-30 degrees C). For the determination of total drug levels (lactone plus lactone ring-opened form), plasma samples were deproteinated with methanol and subsequently acidified with 2% (v/v) perchloric acid. The samples were analysed by HPLC using a Zorbax SB-C18 Stable Bond column and methanol-0.1 M hexane-1-sulfonic acid in methanol-0.01 M N,N,N'N'-tetramethylethylenediamine in distilled water pH 6.0 (25:10:65, v/v/v) as the mobile phase. The detection was performed fluorimetrically. The analytical column was thermostated at 19-21 degrees C to obtain baseline resolution between an interfering endogenous compound in rat and dog plasma and topotecan. This endogenous peak was absent in human plasma. Variation of chromatography temperature appeared to be a very useful tool in the bioanalysis of topotecan. It allowed optimization of the separation between the endogenous compound and the analyte; different mechanisms of solute interactions are apparently involved in this reversed-phase ion-pair chromatographic system.
Animals↗
The use of additives to local anaesthetic solutions for caudal epidural blockade.
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Adrenergic alpha-Agonists↗
Comparison of i.v. and s.c. diamorphine infusions for the treatment of acute pain in children.
We have compared the i.v. and s.c. routes of administration for diamorphine infusions in children undergoing abdominal surgery. Subjects received general anaesthesia with extradural block and diamorphine up to 20 micrograms kg-1 h-1 after operation. There were no differences between the groups in diamorphine consumption, pain scores or incidence of side effects. The s.c. route appeared to be as effective and safe as the i.v. route for administration of diamorphine infusions in children undergoing elective surgery.
Abdomen↗
Extradural clonidine for postoperative pain relief.
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Adrenergic alpha-Agonists↗
Validation of three paediatric pain scores for use by parents.
Twenty children undergoing general surgery and 20 children undergoing otorhinolaryngological surgery were simultaneously assessed on two occasions by a doctor and a parent using three pain scoring systems. The pain scoring systems used were the Objective Pain Score, a four point numerical score and a 100 mm visual analogue scale. There was a high correlation between the scores given by the doctor and by the parents for all three scoring systems with parents consistently giving slightly higher scores than the doctor. The correlation coefficients for parental and medical pain scores in recovery were 0.77 for the Objective Pain Score, 0.70 for the four point numerical score and 0.69 for the visual analogue scale (p < 0.01). At 1 h after leaving the recovery area the correlation coefficients were 0.81, 0.80 and 0.73 respectively (p < 0.01). These results suggest that parental scoring of pain in children will be useful in future audit and research of analgesic regimens, particularly in day-case surgery.
Analgesics↗
The optimal dose of ketamine for caudal epidural blockade in children.
Sixty boys aged up to 9 years undergoing orchidopexy were randomly allocated to receive one of three solutions for caudal epidural injection: group A received 1 ml.kg-1 of 0.25% bupivacaine with 0.25 mg.kg-1 of preservative-free ketamine, group B received 1 ml.kg-1 of 0.25% bupivacaine with ketamine 0.5 mg.kg-1 and group C received 1 ml.kg-1 of 0.25% bupivacaine with 1 mg.kg-1 of ketamine. Postoperative pain was assessed by means of a modified Objective Pain Score and analgesia was administered if this score exceeded four. The median duration of caudal analgesia was 7.9 h in group A, 11 h in group B and 16.5 h in group C. There were no differences between the groups in the incidence of motor block, urinary retention, postoperative vomiting or postoperative sedation. Group C had a significantly higher incidence of behavioural side effects, including slightly odd behaviour, vacant stares and abnormal effect than groups A and B.
Anesthesia, Caudal↗
Proliferation indexes--a comparison between cutaneous basal and squamous cell carcinomas.
AIMS: To compare differences in cell proliferation indexes and apoptotic indexes between cutaneous basal and squamous cell carcinomas, in an attempt to suggest an explanation for the differences in their biological behaviour. METHODS: Forty cases of cutaneous basal cell carcinoma (BCC) and 40 cases of moderately and well differentiated squamous cell carcinoma (SCC) were retrieved from the archives. Sections, 4 microns thick, were cut from formalin fixed, paraffin wax embedded tissue in each case and stained with haematoxylin and eosin. These were then examined for mitotic and apoptotic figures per 1000 cells. Sections from the same cases were also immunostained with the mouse monoclonal antibody Ki67 (MIB1); positive nuclear staining was counted per 1000 cells. RESULTS: No significant differences were found between the mitotic indexes and apoptotic indexes in these tumours. There was, however, a significant difference in Ki67 (MIB1) staining, with greater staining in the squamous cell carcinomas. CONCLUSION: Estimation of the mitotic and apoptotic indexes did not reveal any differences between these two tumour types. The proliferation indexes, assessed by Ki67 immunostaining, did differ. This may be one of the factors underlying the more aggressive behaviour of SCC.
Apoptosis↗