Kathleen R. Rosen

Caudal epidural morphine for control of pain following open heart surgery in children.

The safety and efficacy of epidural morphine injected into the caudal space for control of postoperative pain following open cardiac surgery in children was studied. Thirty-two children between the ages of 2-12 yr for whom early postoperative tracheal extubation was anticipated were randomly assigned to control and study groups. Study subjects received a caudal injection of preservative free morphine sulfate (0.075 mg/kg) in preservative-free normal saline (5-10 ml) following completion of surgery, but prior to awakening and extubation of the trachea. Supplemental intravenous morphine administration and pain scores were recorded for 24 h. Patients in the study group received significantly less (P less than 0.03) morphine (0.32 mg.kg-1.24 h-1) and had significantly lower pain scores than did patients in the control group (0.71 mg.kg-1.24 h-1). The mean duration of complete analgesia in patients receiving caudally administered morphine was 6 h (range 2-12), but decreased analgesic requirements were noted for the entire 24 h. No respiratory depression was evident by clinical variables or repeated arterial blood gas values. Nausea without vomiting occurred in 4/16 patients in the study group. No patient described pruritus. The authors were unable to evaluate the occurrence of urinary retention because all patients had indwelling urinary catheters. They found caudal epidural morphine to be safe and effective in the treatment of postoperative pain in children following open heart surgery.

Nonsteroidal Anti-Inflammatory Agents in Neonates

The use of NSAIDs has become routine for adults and children in the management of pain. NSAIDs (other than aspirin [acetylsalicylic acid]) are also enjoying greater popularity as antipyretics since the recognition of Reye’s syndrome’s putative association with aspirin. In neonates, NSAIDs have been used for many years in an attempt to pharmacologically close the ductus arteriosus. This review examines the various NSAIDs and their potential and real applications in the neonatal population. For completeness, acetaminophen (paracetamol), which has weak NSAID activity and is a widely used analgesic and antipyretic in this patient group, was also included.The prostaglandin system is important for healthy development, and conversely there are unique risks posed by pharmacologic interference with this system in the neonatal period. The prostanoid system in neonates has the capacity to modulate nociception, but comes at the expense of interfering with nearly every organ system. Physiologic effects of inhibition of prostaglandin synthesis applicable to neonates include disruption of the sleep cycle, increased risk of pulmonary hypertension, alterations in cerebral blood flow, decreased renal function, disrupted thermoregulation, and alterations in hemostasis balance, among others. Prostaglandins are also important for the normal development of the central nervous, cardiovascular, and renal systems, and there is evidence that the proper genesis of these systems may be adversely effected by NSAID exposure in utero and in the neonatal period.Gastrointestinal adverse effects have provided the impetus for the development and marketing of selective cyclo-oxygenase type 2 (COX-2) inhibitors. These agents’ reputation for safety in adults may not be applicable to neonates. COX-2 is involved in the development of several organ systems, and its inhibition may induce a prothrombotic state. The advent of parenteral formulations of cyclo-oxygenase inhibitors, including COX-2-selective agents, increases the therapeutic flexibility of NSAIDs. However, objective data on the safety of these agents have not kept pace with their clinical availability.

Continuous intravenous midazolam infusion for sedation in the pediatric intensive care unit

Sedation of intubated spontaneously breathing children in the pediatric intensive care unit is desirable yet often difficult to achieve. A technique for providing consistent sedation in this situation has not been identified. Midazolam is an imidazobenzodiazepine with rapid onset of action and short duration that has been used successfully for sedation in pediatrics (1-4). The pharmacokinetics of midazolam allow the drug to be used as a continuous intravenous intusion (5-1 1). Continuous midazolam infusion with concurrent morphine sulfate infusion has been show7n effective in mechanically ventilated children after cardiac surgery (10,ll). Combining a narcotic aides in sedation but adds undesirable side effects inherent to opioids. The purpose of this paper is to report on the use of midazolam for sedation in intubated spontaneously breathing children in the absence of opioids or other sedatives.

Elimination of drugs and toxins during cardiopulmonary bypass

Cardiopulmonary bypass (CPB) creates a myriad of pharmacological and physiological changes. Some of these changes have been studied in isolated in vitro studies. Integrating an in vitro system into an in vivo process is so complicated that many pharmacological studies simply avoid the bypass period. For the most part, the studies that do examine the bypass period deal with a single drug, reporting how it does or does not produce a predicted concentration on initiation, maintenance and termination of CPB. Based on the isolated results of these studies, this review hypothesizes a model that explains how different substances interact with the CPB system. A summary of the reviews findings include the following: 1) drugs with a smaller volume of distribution are more likely to be effected; 2) the pharmacokinetic effects of lipophilic drugs undergo more alterations than hydrophilic drugs; and 3) protein binding minimizes alterations of lipophilic drugs and increase alterations of hydrophilic drugs.

Analgesia for pediatric thoracostomy tube removal

Eutectic mixture of local anesthetics (EMLA®; Astra Pharmaceuticals, Wayne, PA) has been shown to reduce the pain of blood draws in children. We investigated the use of EMLA® versus IV morphine for providing analgesia during chest tube removal (CTR) in children. One hundred twenty pediatric cardiothoracic surgery patients were enrolled. Patients were randomly assigned to receive either morphine (0.1 mg/kg up to 10 mg IV 30 min before CTR) or EMLA® cream (5 g per chest tube cutaneously 3 h before CTR). A single, trained observer rated the patient’s pain before, during, and after CTR using a 10-cm visual analog scale. The sites were evaluated for adverse effect. Methylhe-moglobin levels were monitored in infants. Before CTR, the pain scores of the children who received morphine were rated lower than those who received EMLA® (P < 0.01). During CTR, there was no difference in the pain score between the morphine or EMLA® group. The change from baseline pain score in the morphine group was significantly larger than in the EMLA® group (P < 0.01). We conclude that EMLA® is safe and useful for blunting the pain of CTR. Implications Chest tube removal is one of the most painful parts of the cardiothoracic surgical experience. This study compared EMLA® (Astra Pharmaceuticals, Wayne, PA) >

Nesiritide during extracorporeal membrane oxygenation.

Nesiritide is a recombinant formulation of B‐type natriuretic peptide (BNP). Preliminary experience in the adult population has shown nesiritide to be an effective agent in the treatment of decompensated congestive heart failure (CHF) in adults. Given its physiological effects, it may be an effective agent in other clinical scenarios. We report the use of nesiritide in two infants during extracorporeal membrane oxygenation (ECMO). In one patient, nesiritide in doses up to 0.09 μg·kg−1·min−1 were used to control mean arterial pressure while in the other patient, doses of 0.01–0.03 μg·kg−1·min−1 were used to augment urine output. The potential applications of nesiritide and dosing regimens for this agent in the ECMO population are discussed.

Fentanyl uptake by the scimed membrane oxygenator.

With the initiation of cardiopulmonary bypass (CPB), using a membrane oxygenator, the drop in circulating fentanyl concentration is greater than can be attributed to dilution alone. This study examined the Scimed brand (2A-800) membrane oxygenator as a site of fentanyl binding. Initial experiments used an assembled CPB circuit. Subsequent dissection and analysis of the oxygenator revealed that the silicone-based membrane sheets were the primary site of fentanyl binding. The silicone-containing waterproof wrapper was also responsible for 1% to 2% of fentanyl binding. Binding of fentanyl to the Scimed membrane oxygenator occurs at a rapid rate and continues until the membrane has taken up 130 ng/cm2 of membrane surface area. The interaction is complete by 15 to 30 minutes if suprasaturated concentrations are used. Samples of membrane material with a surface area of 1 cm2 were also studied. Isolated membrane squares in a nonmoving prime solution required two hours for saturation at the same fentanyl concentrations as the intact membrane with circulating prime. Introduction of motion to the priming solution accelerated the rate of fentanyl binding by the isolated membrane squares to a rate similar to the intact membrane. Motion also provided results similar to those previously reported using different analysis techniques. Therefore, this method of studying fentanyl-membrane interactions using samples of membrane and tritiated fentanyl is a valid model for the intact membrane oxygenator in the assembled bypass circuit. In addition to solution movement, fentanyl concentration of the priming solution was also found to affect the rate of fentanyl uptake. When fentanyl concentrations were used which were insufficient to achieve saturation of the membrane (10 ng/mL and 20 ng/mL), the rate of uptake was slowed. Binding of all available fentanyl under these conditions occurred within three hours. There is potential modification of this interaction by several clinically relevant factors, including temperature, pH, protein content of prime solution, and other drugs. These areas require further study before the saturation data are applied to clinical practice.

Outpatient sedation: An essential addition to gynecologic care for persons with mental retardation

Routine gynecologic care for persons with mental retardation may be difficult to provide, especially to those women who do not allow a pelvic examination to be performed. Of 275 women referred to a multidisciplinary clinic addressing the reproductive health concerns of mentally retarded women, 61 patients (22%) did not allow a gynecologic examination to be performed. The administration of ketamine alone, midazolam alone, or a combination of midazolam and ketamine allowed for the successful performance of a gynecologic examination in 81% of previously uncooperative women. No adverse effects of the medications were noted. We conclude that sedation of difficult-to-examine, mentally handicapped women can be safely performed in the outpatient setting, thus avoiding the need for general anesthesia and its inherent risks.

Comparative flow rates for small bore peripheral intravenous catheters.

The ability to deliver fluid to the pediatric patient is a function of many variables. In addition to patient specific factors such as patient age, size, and weight, and venous size, number, and character, there exist further universal limitations inherent in the equipment which is utilized. Mechanical variables include cannula number, length, brand, and gauge; tubing length, band, style, and gauge; use of extensions; and presence and type of pressure system. This study evaluated a few of these variables. The flow rates were determined for 10 brands of 20-, 22-, and 24-gauge peripheral intravenous catheters. The catheter brands were divided into two groups, slow or faster. The differences in flow between the two categories were statistically significant. The disparities between the slowest and most rapid catheters of the same gauge were only 6.6, 5.4, and 7.7 ml/ min for the 20, 22, and 24 gauges, respectively. The tubing apparatus was also a significant determinant of flow. The addition of any extensions further decreased flow. The magnitude of this slowing was a function of both the tubing and the type of extension

Nalmefene to Prevent Epidural Narcotic Side Effects in Pediatric Patients: A Pharmacokinetic and Safety Study

Study Objective. To determine the pharmacokinetics and preliminary efficacy of nalmefene in children in preventing epidural‐induced narcotic side effects.