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Biomedical subjects

Ralph A Lugo

Publications and source records attributed to Ralph A Lugo.

13 recordsLinked to original sources

Cardiovascular drugs for the newborn.

This article reviews the various cardiovascular drugs for newborns, including antiarrhythmics, antihypertensives, inotropes, and pulmonary vasodilators. Antiarrhythmic drugs are classified according to their mechanisms of action, such as effects on ion channels, duration of repolarization, and receptor interaction, which help with understanding the effects of individual antiarrhythmic drugs and selection of drugs for specific arrhythmias. Drug treatment for hypertension should start with a single drug from one of the following classes: ACE inhibitors, angiotensin-receptor antagonists, beta-receptor antagonists, calcium channel blockers, or diuretics. The inotropic drug should be selected according to its specific pharmacologic properties and the specific cardiovascular abnormality to be corrected. An effective pulmonary vasodilator must dilate the pulmonary vasculature more than the systemic vasculature.

Cardiovascular Agents↗

Failure of nasogastric omeprazole suspension in pediatric intensive care patients.

OBJECTIVES: To determine the efficacy of nasogastric administration of omeprazole suspension in raising the gastric pH >4 in critically ill pediatric patients and to determine the most appropriate dosing regimen for this indication. DESIGN: Open-label pharmacodynamic study. SETTING: Twenty-six bed tertiary-care pediatric intensive care unit. PATIENTS: Mechanically ventilated children aged 1-18 yrs with an additional risk factor for stress ulcer formation. INTERVENTIONS: Continuous gastric pH monitoring was performed during administration and dose titration of omeprazole suspension to achieve the goal of gastric pH >4 for greater than 75% of the dosing interval. MEASUREMENTS AND MAIN RESULTS: Data were collected from 18 patients. Subjects were categorized based on the pharmacologic response to nasogastric administration of 1 mg/kg omeprazole suspension (maximum 20 mg) as rapid (n = 9), late (n = 5), and nonresponders (n = 4). Rapid responders required 0.72 mg/kg per day omeprazole suspension to achieve adequate gastric pH elevation for stress ulcer prophylaxis. Late responders required 1.58 mg/kg per day. Nonresponders did not achieve adequate elevation of gastric pH for stress ulcer prophylaxis. CONCLUSIONS: Nasogastric administration of omeprazole suspension has variable efficacy in critically ill pediatric patients. Half of the studied subjects either required significant dose titrations to achieve gastric acid suppression or did not respond to nasogastric administration of omeprazole suspension.

Administration, Intranasal↗

Pharmacokinetics of methadone.

Methadone is a synthetic opioid that is effective for the relief of moderate-to-severe pain and for the treatment of opioid dependence. The pharmacokinetics of methadone differ from those of morphine in that methadone has a higher bioavailability, a much longer half-life, and is hepatically metabolized by cytochrome P450 enzymes. The pharmacokinetics of methadone are variable and an understanding of the factors that impact the onset, magnitude, and duration of analgesia is required to optimize therapy. Drug interactions are common and patients receiving methadone should be monitored closely for toxicity or therapeutic failure. Special populations in whom a change from the usual dosage regimen may be necessary include pediatric patients, patients with renal failure, the elderly, and pregnant women. To achieve an optimal dosage regimen, the clinician must have an understanding of the pharmacokinetics and pharmacodynamics of methadone in addition to the relationship between these variables and their patients' demographic and pathophysiologic characteristics. AMEDLINE search was performed to identify literature published between 1966 and May 2005 relevant to the pharmacokinetics of methadone. These publications were reviewed and the literature summarized regarding unique and clinically important elements of methadone disposition including its absorption profile, distribution, and metabolism/excretion. General dosing guidelines, dosage conversions from other opioids and pharmacokinetic issues in special populations are discussed.

Aged↗

Postoperative opiate analgesia requirements of smokers and nonsmokers.

BACKGROUND: Smoking cigarettes and other forms of nicotine administration appear to blunt the perception of pain. Abrupt discontinuation of nicotine in nicotine-dependent patients appears to increase the perception of pain. The clinical importance of nicotine's effect on pain perception is not fully understood. OBJECTIVE: To determine whether smokers who abruptly discontinue smoking as a result of being hospitalized for coronary artery bypass graft (CABG) require more postoperative opiate analgesics than nonsmokers. METHODS: A retrospective review of patients who underwent a CABG was performed. Smokers (n = 20) were compared with nonsmokers (n = 69) with regard to opiate analgesic use during the first 48 hours postoperatively. The use of nonopiate sedatives was also compared between the groups. RESULTS: When normalized for weight and body mass index, smokers required 23% and 33%, respectively, more opiate analgesics than did nonsmokers (p = 0.027 and 0.023, respectively). The percentage of patients who received benzodiazepines postoperatively was similar in the 2 groups. CONCLUSIONS: In this study, smokers deprived of nicotine required a greater amount of opiates in the first 48 hours after CABG than did nonsmokers. Healthcare providers need to be aware of the potential for increased narcotic requirements among nicotine-deprived smokers. Further study is needed to determine whether nicotine replacement lessens the requirement for postoperative analgesics in smokers.

Aged↗

Effect of perioperative administration of ropivacaine with epinephrine on postoperative pediatric adenotonsillectomy recovery.

OBJECTIVES: To determine whether perioperative administration of ropivacaine hydrochloride with epinephrine decreases postoperative pain following adenotonsillectomy and to determine the pharmacokinetics of ropivacaine following injection. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: University pediatric ambulatory center. PARTICIPANTS: A total of 130 children, aged 2 to 12 years, undergoing adenotonsillectomy. INTERVENTION: Patients received injections, in the tonsillar fossae, of isotonic sodium chloride solution or 0.5% ropivacaine hydrochloride with epinephrine immediately following tonsillectomy. MAIN OUTCOME MEASURES: Modified objective pain score, time to 100 mL of oral intake, serial plasma ropivacaine levels, use of analgesics, incidence of retching and emesis, and other symptoms. RESULTS: Fifty-three patients (80%) in the ropivacaine group had detectable plasma levels in at least 3 of the 4 measurement time periods. The mean +/- SD peak concentration (C(max)) was 0.71 +/- 0.33 micro g/mL and the half-life was 0.96 hours. The average modified objective pain scores over all time points favored the placebo group (P =.06 test of between-subjects effects). Similarly, the average behavior score over time favored the placebo group (P =.046 test of between-subjects effects). Neck pain was better in the placebo group when averaged over postoperative days 1, 3, 7, and 14 (P =.04). The percentage of patients who had retching in the recovery room was greater in the ropivacaine group (41% vs 19%, P =.006). CONCLUSIONS: The injection of 0.5% ropivacaine with epinephrine immediately following adenotonsillectomy results in a measurable plasma level. Ropivacaine with epinephrine injection does not reduce pain postoperatively and adversely affects behavior scores, neck pain scores, and retching frequency compared with placebo. Ropivacaine with epinephrine injection for postoperative analgesia is not recommended for this patient population.

Adenoidectomy↗

The pharmacokinetics of the intravenous formulation of fentanyl citrate administered orally in children undergoing general anesthesia.

The bioavailability of oral transmucosal fentanyl citrate (OTFC) in children is similar to that of fentanyl solution administered orally to adults. We hypothesized that administering an oral fentanyl solution to children would result in similar fentanyl plasma concentrations and pharmacokinetic variables as administering comparable doses of OTFC. In this pilot study, 10 healthy children requiring postoperative analgesia were enrolled. Each received the undiluted IV fentanyl formulation orally (approximately 10-15 microg/kg; maximum, 400 microg). Venous blood samples were collected from 15 to 600 min after administration. Pharmacokinetic variables were determined using noncompartmental analysis and were compared with a previously studied population of children who received a similar dose of OTFC. Pharmacokinetic variables for the orally administered IV fentanyl formulation were as follows: time to reach peak concentration = 1.7 +/- 1.6 h, peak concentration = 1.83 +/- 1.19 ng/mL, half-life = 4.7 +/- 2.8 h, area under the plasma concentration time curve = 6.46 +/- 3.96 h . ng(-1) . mL(-1), apparent oral volume of distribution (V/F) = 17.5 +/- 7.2 L/kg, apparent oral clearance (CL/F) = 3.33 +/- 2.25 L . kg(-1) . h(-1). Although both OTFC and orally administered IV fentanyl resulted in similar pharmacokinetic variables and plasma concentrations for a given dose, there was marked interpatient variability, particularly in the early hours after oral administration of the IV formulation of fentanyl. This suggests that this method of administration be used with caution until further data are available.

Administration, Oral↗

The pharmacokinetics of oxycodone.

Oxycodone is among the most commonly used opioid analgesics for the relief of moderate-to-severe pain and is pharmacodynamically comparable to morphine. Oxycodone is available in the United States in oral dosage forms and controlled-release tablets. Studies have demonstrated marked interindividual variation in the pharmacokinetics of oxycodone. The pharmacokinetics of oral oxycodone differs from oral morphine in that it has a higher bioavailability, a slightly longer half-life, and is hepatically metabolized by cytochrome P450 rather than undergoing glucuronidation. Understanding oxycodone pharmacokinetics favors safe and effective use of this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and May 2004 relevant to the pharmacokinetics of oxycodone. These publications were reviewed and the literature summarized regarding unique and clinically important elements of oxycodone disposition including its absorption profile (immediate release, controlled release, rectal administration, and intranasal administration), distribution, and its metabolism/excretion. Special populations, including children and those with liver/renal failure, have a unique oxycodone pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.

Administration, Oral↗

Albuterol delivery from a metered-dose inhaler with spacer is reduced following short-duration manual ventilation in a neonatal ventilator-lung model.

INTRODUCTION: Albuterol aerosol is commonly administered to mechanically ventilated neonates via metered-dose inhaler (MDI) with spacer. The spacer increases the dead space in the ventilation circuit, and some institutions limit the amount of time the spacer remains in line, to minimize carbon dioxide retention and the risk of hypercarbia. However, minimizing the amount of time the spacer remains in line might also limit albuterol delivery to the patient. OBJECTIVE: To determine whether limiting the amount of time the spacer is left in line after MDI actuation significantly reduces albuterol delivery. METHODS: We conducted a bench study with a neonatal ventilator-lung model that included a Bird VIP ventilator, in a time-cycled, pressure-limited, continuous-flow mode, with settings to simulate a 1-kg infant with moderate lung disease: peak inspiratory pressure 25 cm H2O, positive end-expiratory pressure 4 cm H2O, respiratory rate 30 breaths/min, inspiratory time 0.35 s, tidal volume approximately 7 mL. The circuit was attached to a 3.0-mm inner-diameter endotracheal tube and a neonatal test lung. We tested 5 methods of MDI albuterol administration. The first 3 methods used a spacer attached to the ETT and either 5, 15, or 30 manual breaths (flow 6 L/min, respiratory rate 30 breaths/min, peak inspiratory pressure 25 cm H2O) were delivered after each MDI actuation (2 actuations). The final 2 methods used an in-line spacer (placed between the circuit Y-piece and the endotracheal tube) with the spacer kept in line for 30 or 60 s after each actuation (2 actuations). A breathing filter was placed between the ETT and test lung to trap the aerosolized albuterol. RESULTS: Mean +/- SD albuterol delivery was 2.3 +/- 0.5%, 3.6 +/- 1.8%, and 5.1 +/- 1.3% after 5, 15, and 30 manual breaths, respectively (p < or = 0.05 for 30 breaths vs 5 and 15 breaths). Albuterol delivery was 3.7 +/- 1.3% when the spacer was left in line for 30 s, versus 3.7 +/- 0.6% when it was left in line for 60 s. CONCLUSIONS: Limiting the time that the spacer was left in line after each MDI actuation significantly reduced albuterol delivery in our neonatal ventilator-lung model.

Administration, Inhalation↗

Clinical pharmacokinetics of morphine.

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.

Administration, Oral↗

Chronically inhaled salmeterol improves pulmonary function in heart failure.

Inhaled beta-agonists are commonly prescribed for the symptoms of exercise intolerance in heart failure despite a paucity of data regarding their safety and efficacy. This was a prospective, randomized, double-blind, double-dummy, placebo-controlled 14-day cross-over study to determine if chronic inhaled salmeterol therapy 84 microg every 12 hours improved pulmonary function without augmentation of neurohormonal systems or ventricular ectopy in 8 symptomatic heart failure subjects with left ventricular ejection fraction (LVEF) <40% and FEV1 <or=80%. The primary endpoint was FEV1, and the secondary endpoints were forced vital capacity (FVC), forced expiratory flow (FEF25-75), peak expiratory flow rate (PEFR), blood pressure, heart rate, rate-pressure product, plasma norepinephrine, plasma epinephrine, plasma renin activity, percent ventricular ectopy, and salmeterol pharmacokinetics. Salmeterol was associated with a significant 6% improvement in FEV1 compared with placebo (salmeterol 2.46 +/- 0.73 vs. placebo 2.33 +/- 0.73 L, p = 0.01). There was no significant difference in FVC, FEF25-75, and PEFR. Salmeterol increased mean rate-pressure product by 5% (salmeterol 8878 +/- 1560 vs. placebo 8414 +/- 1440 bpm x mm Hg, p = 0.04), although no increase in plasma norepinephrine, epinephrine, plasma renin activity or ventricular ectopy was detected. The Tmax, Cmax, and half-life of salmeterol at steady-state were 5 min, 715 pg/ml and 11.4 hours, respectively. Inhaled salmeterol significantly improves FEV1 without producing measurable effects on neuroactivation or ventricular ectopy. Inhaled salmeterol causes minor increases in rate-pressure product, whose clinical significance remains to be determined. The plasma half-life of salmeterol may be prolonged in heart failure patients, thus leading to accumulation at steady-state.

Administration, Inhalation↗

A survey of albuterol administration practices in intubated patients in the neonatal intensive care unit.

INTRODUCTION: Aerosolized albuterol is commonly used in the treatment of neonatal respiratory illnesses. Clinical and in vitro studies have identified numerous factors that affect aerosol drug delivery during neonatal mechanical ventilation, including the choice of metered-dose inhaler (MDI) or nebulizer, the use of a holding chamber, time between actuations, the volume of nebulized solution, and the position and placement of the nebulizer or MDI. Because there is no consensus on the optimal method of administration, there is probably substantial variability among institutions in how aerosolized albuterol is administered to mechanically ventilated infants in the neonatal intensive care unit (NICU). OBJECTIVE: Survey academic medical centers in the United States regarding their practices of administering aerosolized albuterol to intubated newborns in the NICU. METHODS: A survey instrument was developed that queried 18 aspects of albuterol administration in mechanically ventilated infants, including the frequency of MDI and nebulizer use, the average and maximum dose, the time between MDI actuations and following the final actuation, the use of a holding chamber, and the placement location of the holding chamber or nebulizer. Respiratory therapists and respiratory therapy managers having direct knowledge of neonatal clinical practices in their neonatal fellowship program NICUs were surveyed via telephone. Those who did not respond via telephone were surveyed via fax. RESULTS: Eighty institutions were surveyed and there were 68 respondents (85% response rate). Responders averaged 35 +/- 13 NICU beds and 11 +/- 5 ventilators/d. Nineteen percent of the respondents reported administering albuterol via MDI 100% of the time; 22% use MDIs 75-99% of the time; 9% use MDIs 50-74% of the time; 4% use MDIs 25-49% of the time; and 43% never use MDIs to deliver albuterol. The average dose via MDI was: 1 puff: 30%; 2 puffs: 65%; and 4 puffs: 5%. The maximum dose via MDI was: 2 puffs: 30%; 3 puffs: 14%; 4 puffs: 36%; 6 puffs: 11%; and 8 puffs: 6%. Thirty-one percent of the respondents place the holding chamber in-line with the ventilator circuit, 56% administer the aerosol via manual ventilation, and 13% use both methods. Fifty-six percent place the in-line holding chamber between the endotracheal tube and ventilator circuit, and the other 44% place the in-line holding chamber in the inspiratory limb. The time between MDI actuations depended on whether the holding chamber was placed in-line or the aerosol was administered via manual ventilation (MV): < or = 0.5 min: 18% in-line and 28% MV; 1 min: 47% in-line and 43% MV; 2 min: 6% in-line and 4% MV; 3 min: 6% in-line and 0% MV. Eighty-three percent of respondents indicated that dead space introduced by a holding chamber/spacer was not a concern. Forty-three percent use nebulizers exclusively to administer albuterol to mechanically ventilated patients. Seventy-four percent of centers that nebulize albuterol use a dose of 1.25-2.5 mg. Eighty-eight percent of the surveyed institutions place nebulizers in-line with the ventilator circuit, and the other 12% use manual ventilation to administer the nebulized aerosol. Of those that use in-line nebulization, 95% place the nebulizer in the inspiratory limb of the circuit, and the other 5% place the nebulizer between the endotracheal tube and circuit Y-piece. Among centers that place the nebulizer in the inspiratory limb, 52% place it adjacent to the circuit Y-piece, 36% place it midway upstream in the inspiratory limb, and 12% place it near the humidifier. CONCLUSION: There is substantial variability among NICUs in albuterol administration to mechanically ventilated infants, with the majority of institutions now administering albuterol via MDI.

Academic Medical Centers↗