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Biomedical subjects

C B Berde

Publications and source records attributed to C B Berde.

At least 37 records · Page 2Linked to original sources
PubMed1996

NG-nitro-L-arginine methyl ester (L-NAME) prevents tachyphylaxis to local anesthetics in a dose-dependent manner.

A model of local anesthetic tachyphylaxis was developed in our group previously using repeated sciatic nerve blocks in rats. In this model, thermal hyperalgesia accelerated tachyphylaxis, and the noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, MK-801, prevented both hyperalgesia and tachyphylaxis. Nitric oxide is thought to be a second messenger for NMDA pathways in the spinal cord, and appears to be involved in spinal mechanisms of hyperalgesia. We hypothesized that nitric oxide synthase inhibitors would also inhibit the development of tachyphylaxis. Repeated rat sciatic nerve blocks were placed by percutaneous injection of 2-chloroprocaine. Block duration was tested by measuring hot-plate latency at 56 degrees C. Two hours before the first nerve block, rats received intraperitoneal injections with saline or one of six concentrations of NG-nitro-L-arginine methyl ester (L-NAME) in a randomized, blinded pattern. Control rats developed tachyphylaxis as seen previously: the duration of the third block was 30% that of the first. L-NAME inhibited the development of tachyphylaxis in a dose-dependent manner; tachyphylaxis was inhibited by 50% using L-NAME at 0.2mg/kg and completely abolished by 50 mg/kg. Nitric oxide pathways may be involved in the development of tachyphylaxis to local anesthetic nerve block.

Anesthetics, Local↗
PubMed1996

Halothane and cardiac autonomic control in infants: assessment with quantitative respiratory sinus arrhythmia.

In comparison to adults, infants undergoing halothane anesthesia have an increased incidence of clinically significant episodes of bradycardia, hypotension, and cardiac arrest. To examine potential cardiac autonomic regulatory mechanisms that may account for these observations, the relationship between respiratory activity and short-term variations of heart rate was quantified in 10 healthy term nonpremedicated infants (28.4 +/- 0.6 wk old) undergoing elective surgery with halothane and low caudal anesthesia. Quantitative respiratory activity, heart rate, and cuff blood pressure data were obtained during the preoperative awake period, and at three depths of halothane--1, 1.3, and 2.0 mean alveolar concentration (MAC). Time and frequency domain analyses were performed on two 2.2-min epochs of data from each condition to yield mean values, spectral measures of low (0.02-0.15 Hz) and high (0.15-0.80 Hz) frequency power (LF and HF), and the LF/HF ratio. The sympathetic (As) and parasympathetic (Ap) components of respiratory sinus arrhythmia were quantified using the transfer relations between respiration and heart rate to derive gain factors Ax and Ap, respectively. Mean heart rate, blood pressure, and respiratory activity all decreased with halothane exposure (p < 0.01), but did not differ by halothane dose. Similarly, LF, HF, LF/HF, and respiratory powers all decreased with halothane, but not between doses. When the effects of respiratory activity on heart rate were accounted for, As decreased at 1.3 and 2.0 MAC only, but Ap remained unchanged. Decreased LF and HF power suggests that halothane altered both sympathetic and parasympathetic heart rate control; however, when the ratio between LF and HF and the quantitative effects of respiration are accounted for, halothane appears to cause a reduction in respiratory related sympathetic heart rate control, without a significant change in parasympathetic control.

Anesthetics, Inhalation↗
PubMed1996

Chronic pain in cystic fibrosis.

OBJECTIVE: The objective of this study was to examine the incidence and therapy of chronic pain in a group of older patients with cystic fibrosis (CF). PATIENTS: We identified two groups of patients followed at the CF Center at Children's Hospital (Boston); the first group consisted of all patients above the age of 5 years who died between 1984 and 1993, and the second was a cohort of 23 additional CF patients who had been referred to the Pain Treatment Service. DESIGN: Medical charts were reviewed for the etiology and therapy of all pain episodes requiring medical intervention. RESULTS: The incidence of chronic pain in this population increased sharply in the last 6 months of life. Headaches (55% of patients) and chest pain (65%) were frequently reported, although back pain (19%), abdominal pain (19%), and limb pain (16%) were also reported. In patients with headache, the main etiologies were hypercarbia or hypoxia, migraine, and sinusitis. The majority of chest pain was musculoskeletal, with pleuritis, pneumothorax, and rib fracture also reported as the cause of chest pain. INTERVENTIONS: A variety of nonpharmacological and pharmacological therapies were reported. Forty-one patients (53%) had pain severe enough to require opioid treatment, and 10 patients (13%) received opioids for more than 3 months. In eight patients with more severe pain, regional analgesia was found to be particularly effective. CONCLUSIONS: Chronic pain is a common problem in CF, particularly as the patient population ages. When administered with caution, opioids have proven to be effective and safe in this population; regional anesthesia can be used to preserve pulmonary toilet while adequately treating severe pain.

Adolescent↗
PubMed1995

Intravenous amitriptyline in pediatrics.

Oral amitriptyline has been used as an analgesic in a wide range of pain settings. Despite long-term availability of a parenteral form, the few reports about this formulation have been limited to pharmacokinetic studies in normal volunteers, trials in depressed patients, and analyses of electroencephalogram (EEG) activation. We retrospectively reviewed our experience using intravenous (IV) amitriptyline at Children's Hospital, Boston and at Children's Hospital at Stanford. Eight children (aged 5-16.6 years), who were unable to tolerate medications by the oral route, received IV amitriptyline for a variety of indications, including neuropathic pain, depression, sleep disturbance, and as an adjuvant agent for opioid analgesia. One patient experienced an extrapyramidal reaction temporally related to the administration of IV amitriptyline, which was successfully managed with diphenhydramine. Further prospective, controlled studies are needed to further assess the safety, efficacy and tolerability of this novel use of amitriptyline.

Adolescent↗
PubMed1995

Control of severe pain in children with terminal malignancy.

OBJECTIVE: To identify the characteristics of the subset of children with malignancy in whom massive opioid infusions are needed during the terminal phase. DESIGN: Retrospective review of the records of the 199 patients who died of malignancy after treatment at Children's Hospital, Boston, from March 1989 to July 1993, identifying characteristics of patients who required massive opioid infusions (operationally defined as infusion of > 3 mg/kg per hour of morphine dose equivalent) during the terminal phase. RESULTS: Twelve patients (6%) required massive opioid infusions, and eight of these patients required extraordinary measures (epidural or subarachnoid infusion and/or sedation) to achieve adequate analgesia. The duration of epidural or subarachnoid infusions in three patients ranged from 3 to 9 days, and minimal complications occurred. The duration of sedation ranged from 1 to 15 days. Maximal intravenous opioid dosing ranged from 3.8 to 518 mg/kg per hour of morphine equivalent. The maximal infusion rate (exceeding all previous published reports) occurred in an infant with an isolated metastasis in the periaqueductal gray matter, a brain-stem site linked to mediating analgesia and defense reactions. The need for massive opioid dosing in 11 of 12 patients was associated with tumor spread to the spinal nerve roots, nerve plexus, large peripheral nerve, or spinal cord compression. CONCLUSIONS: Standard dosing of opioids adequately treats most cancer pain in children; however, a significant group requires more extensive management. These problems occur more commonly among patients with solid tumors metastatic to spine and major nerves.

Adolescent↗
PubMed1995

Infants tolerate spinal anesthesia with minimal overall autonomic changes: analysis of heart rate variability in former premature infants undergoing hernia repair.

Unlike adults, neonates tolerate high thoracic spinal anesthesia with minimal changes in heart rate (HR) and arterial blood pressure. To examine the potential autonomic regulatory mechanisms which may account for these findings, the relation between short-term heart rate variability (HRV) and respiratory activity was analyzed in a group of eight ASA grade II former premature infants undergoing high thoracic spinal anesthesia for inguinal hernia repairs. Quantitative measures of sympathetic (As) and parasympathetic (Ap) modulation of HR were derived. HR, arterial blood pressure, and a calibrated respiratory signal were recorded during 4.4-min stable epochs in eight subjects 1) preoperatively, 2) postincision after high thoracic spinal anesthesia, and 3) during an active sleep state in the postoperative period. Power spectral analysis of HRV and respiratory power yielded measures of low-frequency power (LFP: 0.02-0.15 Hz) and high-frequency power (HFP: 0.15-0.8 Hz). Transfer function analysis between respiratory activity and HR were used to quantify As and Ap. All subjects had successful high thoracic spinal anesthesia with highest levels ranging from C7-T4. Mean HR, blood pressure, and respiratory power did not change significantly with high thoracic spinal anesthesia. LFP and HFP both decreased significantly, whereas the LFP/HFP ratio remained stable. Group mean As and Ap both decreased, but the changes were not significant. Despite overall cardiovascular stability, HRV decreased with high thoracic spinal anesthesia, but the balance between LFP and HFP remained stable, suggesting that the reflex response to high thoracic spinal anesthesia was predominantly diminished parasympathetic modulation of cardiac function. The expected decrease in HR and blood pressure from the sympatholysis which results from high thoracic spinal anesthesia were apparently offset by withdrawal of cardiac vagal activity.

Anesthesia, Spinal↗
PubMed1995

A double-blind evaluation of ketorolac tromethamine versus acetaminophen in pediatric tonsillectomy: analgesia and bleeding.

The study was designed to compare intravenous ketorolac to rectal acetaminophen for analgesia and bleeding in pediatric patients undergoing tonsillectomy. We studied 50 patients, aged 2-15 yr undergoing tonsillectomy with or without adenoidectomy. In a randomized, prospective double-blind fashion, patients were assigned to receive either ketorolac (1 mg/kg) or rectal acetaminophen (35 mg/kg). Bleeding was evaluated by measuring intraoperative blood loss and noting extra measures required to obtain hemostasis. Bleeding times were also measured before and during surgery. Pain was evaluated using a standard objective pain score for the first 3 h. Persistent pain was treated with morphine, acetaminophen, and codeine and recorded for 24 h. Blood for determination of acetaminophen levels was drawn at 20 and 40 min after the administration of study drugs. Pain scores were not significantly different between the ketorolac and acetaminophen groups. The majority of patients in both groups required additional opioid in the postoperative period. Acetaminophen levels were all less than the therapeutic range. Intraoperative bleeding times were normal in all patients, but blood loss was significantly higher in the ketorolac group (2.67 mL/kg) compared to the acetaminophen group (1.44 mL/kg), P = 0.025. Significantly more measures to achieve hemostasis were required in the ketorolac group (P = 0.012). We conclude that ketorolac is no more effective than high-dose rectal acetaminophen for analgesia in the patient undergoing tonsillectomy. Hemostasis during tonsillectomy was significantly more difficult to achieve in patients receiving ketorolac.

Acetaminophen↗
PubMed1995

The risk of infection from epidural analgesia in children: a review of 1620 cases.

We reviewed cases to determine whether suspected or confirmed epidural infection was associated with epidural analgesia for 1620 infants, children, and adolescents treated over a 6-yr period at Children's Hospital, Boston. Postoperative patients (1458/1620) received epidural infusions for a median of 2 days (range, 0-8 days). No postoperative patient had an epidural abscess. One 10-yr-old with terminal malignancy received thoracic epidural analgesia via two successive catheters over a 4-wk period. She had Candida colonization of the epidural space along with necrotic epidural tumor. A second oncology patient and two patients with reflex sympathetic dystrophy were evaluated for epidural abscess, but none was found. We conclude that the risk of epidural infection is quite low in pediatric postoperative patients receiving short-term catheterization. Use of prolonged epidural analgesia in the management of chronic pain in children requires careful monitoring of warning signs of infection.

Abscess↗
PubMed1994

Dextroamphetamine or methylphenidate as adjuvants to opioid analgesia for adolescents with cancer.

The doses of opioid analgesics required to control pain in patients with cancer may result in somnolence and reduced interaction with family members. Psychostimulants such as dextroamphetamine (DA, Dexedrine) or methylphenidate (MP, Ritalin) have been used in adults to counteract the sedation of opioid analgesia. We retrospectively reviewed our experience using these agents at Children's Hospital. Eleven patients (age 12-20 years) received DA or MP, and decreased somnolence or improved interaction was noted in five patients. Adverse effects potentially related to DA or MP were noted in two patients, none of which resulted in discontinuance of the stimulant. Further prospective, controlled studies are needed to assess the safety and efficacy of DA and MP in counteracting the sedation of opioid analgesia in children and adolescents.

Adjuvants, Pharmaceutic↗
PubMed1994

Thermal hyperalgesia accelerates and MK-801 prevents the development of tachyphylaxis to rat sciatic nerve blockade.

BACKGROUND: Tachyphylaxis to local anesthetics has been shown to be promoted by longer interanalgesic intervals between injections. We hypothesized that thermal hyperalgesia also would accelerate the development of tachyphylaxis. The n-methyl-D-aspartate antagonist ((+)-5 methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine, or dizocilpine) (MK-801) has been shown to prevent thermal hyperalgesia. We therefore also hypothesized that MK-801 would prevent tachyphylaxis. METHODS: Catheters were surgically implanted in rats along the sciatic nerve. After recovery and conditioning to the testing paradigm, they received repeated injections of lidocaine or 2-chloroprocaine followed by motor block testing with or without hot-plate testing at 48, 52, or 56 degrees C. In other experiments, MK-801 or saline was administered by intraperitoneal injection before sciatic nerve local anesthetic injection and sensory and motor testing. RESULTS: Rats receiving repeated lidocaine or 2-chloroprocaine injections, when repeatedly subjected to hot-plate testing at 56 degrees C, developed thermal hyperalgesia and tachyphylaxis to motor and sensory blockade. Rats receiving either no hot-plate exposure or hot-plate exposure at 48 degrees C developed no tachyphylaxis or hyperalgesia. Rats tested at 52 degrees C developed milder hyperalgesia and developed tachyphylaxis more slowly than did rats tested at 56 degrees C. Control experiments excluded artifacts due to circadian rhythm, injection volume, and learning. Rats pretreated with MK-801 showed no tachyphylaxis over a series of three injections. CONCLUSIONS: Thermal hyperalgesia accelerates the development of tachyphylaxis to rat sciatic nerve blockade, and MK-801 prevents tachyphylaxis in this model. n-Methyl-D-aspartate receptor antagonists may have future clinical utility in increasing the duration of effectiveness of prolonged local anesthetic administration.

Animals↗
PubMed1993

Toxicity of local anesthetics in infants and children.

Local anesthetics are extremely useful for providing anesthesia and analgesia for infants and children of all ages. Despite the toxicity issues raised here, the overall safety record of local anesthetic use in pediatrics has been very good, and local anesthetic administration within safe guidelines should be encouraged. In the great majority of cases, toxic reactions have been associated with either inadvertent intravascular injection or unintentional overdosage by physicians who did not adequately consider issues related to systemic drug uptake, distribution, or clearance. Unlike opioids, which can be titrated according to clinical signs to a wide range of doses, local anesthetic administration must be strictly limited "by the numbers." Pediatricians, surgeons, emergency room physicians, and anesthesiologists need to be informed regarding limits for the administration of local anesthetics and management of toxic reactions.

Absorption↗
PubMed1993

Sustained local anesthetic release from bioerodible polymer matrices: a potential method for prolonged regional anesthesia.

Polyanhydride polymer matrices have been used successfully for sustained release of a number of drugs in vitro and in vivo. Dibucaine free base, dibucaine HCl, and bupivacaine HCl were incorporated into polymer matrices with copolymer 1,3-bis(p-carboxyphenoxy)propane-sebacic acid anhydride (1:4). Drug release was measured in vitro following incubation of the drug-polymer matrices in phosphate buffered solution, pH 7.4, at 37 degrees C, to approximate in vivo conditions. Local anesthetics were released in a sustained manner yielding 90% cumulative drug release over periods ranging from 3 to 14 days. The kinetics of release varied with both the choice of local anesthetic and the method of drug incorporation into the matrix (hot melt versus compression molding). Polymer local anesthetic matrix devices (PLAM), loaded by hot melt incorporation with 20% bupivacaine, were implanted in vivo adjacent to the sciatic nerve in three rats. Reversible neural blockade was observed for 4 days in all animals. Polymer implants without local anesthetic showed no neural blockade. This technology could lead to methods of prolonged blockade of peripheral nerves or of sympathetic ganglia, which may be utilized for the management of postoperative pain, sympathetically maintained pain, or certain forms of chronic pain.

Analysis of Variance↗
PubMed1993

Prolonged regional nerve blockade by controlled release of local anesthetic from a biodegradable polymer matrix.

BACKGROUND: Prolonged nerve blockade is potentially useful in the management of many acute and chronic pain problems. Aside from infusions via an indwelling catheter, most currently available nondestructive techniques for prolonging local anesthetic action cannot provide more than 1-2 days of blockade. Bioerodible polymer matrixes have been used to deliver a variety of drugs in patients and animals for periods lasting weeks to years. Previously, dibucaine and bupivacaine were incorporated into copolymers of 1,3 bis(p-carboxyphenoxy) propane-sebacic acid anhydride (1:4), and demonstrated sustained release in vitro following incubation of the drug-polymer matrixes in phosphate-buffered solution (pH 7.4, 37 degrees C). METHODS: In the present study, cylindrical pellets made from polymer matrixes incorporated with bupivacaine-HCl were implanted surgically along the sciatic nerves of rats. Neural block was assessed by direct observation of motor skills and by leg-withdrawal latency to a hot surface. Biochemical and histologic examinations were performed 2 weeks after implantation. RESULTS: Sensory and motor blockade was produced for periods ranging from 2 to 6 days. Contralateral control legs receiving polymer implants without drug showed no block. Blockade was reversible, and animals appeared to recover sensory and motor function normally. Biochemical indexes of nerve and muscle function were indistinguishable from contralateral controls. CONCLUSIONS: This biodegradable polymer system provides a promising new alternative for the delivery of local anesthetics to peripheral nerves to produce prolonged blockade for the management of acute and chronic pain.

Anesthetics, Local↗
PubMed1993

Intravenous isoproterenol as a marker for epidural test-dosing in children.

The purpose of this study was to determine if isoproterenol would be an effective marker of intravascular injection in anesthetized children. Forty-four ASA 1 children, aged 2 mo to 10 yr, were randomly assigned to two groups. Children in group 1 (n = 21) received 0.05 microgram/kg isoproterenol, and children in group 2 (n = 23) received 0.075 microgram/kg isoproterenol. A blinded observer continuously recorded heart rate and arterial blood pressure. Measurements were recorded before the surgical incision at steady-state halothane concentration of 1.2 minimum alveolar concentration adjusted for age. Isoproterenol produced a graded increase in heart rate with mean maximum increases of 16.5 +/- 8.7 beats/min in group 1 and 21.5 +/- 9.2 beats/min in group 2. No episodes of hypotension and arrhythmia were noted. Isoproterenol, 0.075 microgram/kg, is more sensitive but still is an imperfect marker of an intravascular injection. It produces a heart rate increase in 96% of children anesthetized with halothane and nitrous oxide in 50% oxygen. The application of isoproterenol as an epidural test dose appears promising, but cannot be recommended until its full reliability and neurotoxicity are evaluated.

Anesthesia, Epidural↗
PubMed1993

Performance of pediatric resuscitation bags assessed with an infant lung simulator.

Many pediatric self-inflating bags are equipped with pressure relief (pop-off) valves to prevent barotrauma. We participated in a resuscitation in which a valve malfunction briefly caused inadequate ventilation. The pop-off valve was seated in an intermediate position between open and closed settings. To investigate this problem, we assessed the performance of several commonly used pediatric self-inflating bags using an infant lung simulator (D, B & M, Redlands, CA). Bags were deflated using a range of inspiratory times (TI), delivered tidal volumes, peak proximal airway pressure (Pp), and peak distal pressure (lung pressure, Pd). When the pop-off valve was set in the open position, Pp ranged from 42 cm to 105 cm H2O, although P(d) never exceeded 45 cm H2O. The mean difference between Pp and P(d) decreased from 14.2 +/- 1.1 cm H2O at TI = 0.2 s to 6.1 +/- 0.5 cm H2O at TI = 1 s. Inflation of all DMR (disposable) and PMR (nondisposable) bags in the intermediate valve position produced marked air leakage through the valve, with delivered tidal volumes of only 92 +/- 13 mL (DMR) for TI < 0.5 s, and unrecordable tidal volumes (< 50 mL) for both DMR and PMR self-inflating bags for TI > 0.6 s. A wide range of delivered tidal volumes was observed among all bags examined. We conclude that both DMR and PMR bags can be placed inadvertently in an intermediate valve position that can produce disastrous hypoventilation during resuscitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Equipment Failure↗