Michael Tobin

twenty-four-hour Pharmacokinetics of Rectal Acetaminophen in Children : an Old Drug with New Recommendations

Background: Rectal acetaminophen is often administered during operation to provide supplemental analgesia or antipyresis in children. Recent studies examining current dose guidelines are limited by short sampling times. The authors extended the drug sampling period to more clearly define acetaminophen pharmacokinetics in children having surgery. Methods: Children (n = 28) were randomized to receive a single dose of 10, 20, or 30 mg/kg rectal acetaminophen after induction of anesthesia. Venous blood samples were taken every 30 min for 4 h, every 60 min for 4 h, and every 4 h for 16 h. Data were analyzed using a mixed‐effects modeling technique (using NONMEM software) to determine the volume of distribution and clearance normalized for bioavailability. Additional models accounted for suppository dissolution followed by acetaminophen absorption. Results: Age, weight, estimated blood loss, volume of intravenous fluid administered, and anesthesia time were similar in the three groups. Most patients did not achieve peak or sustained serum values in the 10–20 micro gram/ml serum concentration range associated with antipyresis. The volume of distribution was 385 ml/kg, and clearance normalized for bioavailability, F, was 5.46 ml [center dot] kg sup ‐1 [center dot] min sup ‐1. Pharmacokinetic models suggest that absorption of acetaminophen is a function of zero‐order dissolution of suppositories and first‐order absorption from the rectum. Suppository dose size also may affect absorption characteristics. Conclusions: The current recommended rectal acetaminophen dose of 10–15 mg/kg yields peak serum concentrations less than the antipyretic serum concentration of 10–20 micro gram/ml. Based on the observed kinetics, the authors recommend that the initial dose should be approximately 40 mg/kg.

Initial and subsequent dosing of rectal acetaminophen in Children : A 24-hour pharmacokinetic study of new dose recommendations

Background Recent studies have determined that an initial rectal acetaminophen dose of approximately 40 mg/kg is needed in children to achieve target antipyretic serum concentrations. The timing and amount of subsequent doses after a 40-mg/kg dose has not been clarified for this route of administration. Based on the authors’ previous pharmacokinetic data, they examined whether a 40-mg/kg loading dose followed by 20-mg/kg doses at 6-h intervals maintain serum concentrations within the target range of 10–20 &mgr;g/ml, without evidence of accumulation. Methods Children (n = 16) received rectal acetaminophen (40 mg/kg) and up to three additional doses of 20 mg/kg at 6-h intervals. Venous blood samples were taken every 30 min for 4 h, then every 60 min for 4 h, and every 4 h for 16 h. The authors assessed whether their published pharmacokinetic parameters predicted the acetaminophen concentrations in the present study. They also assessed their dosing regimen by determining the fraction of time each individual maintained the target concentration. Results All patients received the initial loading dose; 10 of 16 patients received three subsequent doses. Serum concentrations with the initial dose were in the target range 38 ± 25% of the time. With subsequent dosing, the target range was maintained 60 ± 29% of the time. The highest serum concentration with initial or subsequent dosing was 38.6 &mgr;g/ml. Pharmacokinetic parameters from the earlier study predicted the serum concentrations observed for both initial and subsequent doses. Conclusions A rectal acetaminophen loading dose of 40 mg/kg followed by 20-mg/kg doses every 6 h results in serum concentrations centered at the target range of 10–20 &mgr;g/ml. There was large interindividual variability in pharmacokinetic characteristics. There was no evidence of accumulation during the 24-h sampling period.

The effect of circuit compliance on delivered ventilation with use of an adult circle system for time cycled volume controlled ventilation using an infant lung model

This in vitro study examined the effect of circuit compliance on delivered ventilation (VE) using a time‐cycled, volume controlled circle system in an infant lung model. A Bio‐Tek ventilator tester set to simulate normal and abnormal lung compliance measured VE delivered by the Narkomed 2B system. Circle circuits of varied compliance (2.75, 1.22 and 0.73 μl·cm H2O−1) were tested. Tidal volume was adjusted to peak inflation pressures (PIP) of 20, 30, 40, and 50 cm H2O with three circuits, two lung compliances, and four different size tracheal tubes (TT) (2.5, 3.5, 4, 4.5 mm ID). Data were analysed using the multiple regression technique. Delivered VE was directly related to PIP and lung compliance. Delivered VE was not affected by the choice of circuit. TT size had minimal effects on VE when lung compliance was low; TT size was a more important factor when test lung compliance was normal. Extrapolating this data to the clinical setting, adequate ventilation of infants can be achieved with an adult circle system if an appropriate PIP is chosen, regardless of the compliance of the circuit used. Infants with poor lung compliance may require very high PIP for adequate ventilation.

A comparison of three modes of ventilation with the use of an adult circle system in an infant lung model

We examined the efficiency of an adult circle system with adult bellows to deliver minute ventilation (VE) to an infant test lung model.A Narkomed 2B system (North American Drager, Telford, PA) using three modes of ventilator setup were used: A = time-cycled, volume-controlled using bellows excursion to control delivered volume; B = time-cycled, pressure-controlled using inspiratory pressure limit adjustment to control delivered volume; C = time-cycled, pressure-controlled using the inspiratory flow adjustment to control delivered volume. VE was measured with two compliances (normal and low) and four endotracheal tube (ETT) sizes (2.5-, 3.0-, 3.5-, and 4.0-mm inner diameter). VE was measured at peak inspiratory pressures (PIP) of 20, 30, 40 or 50 cm H2 O while respiratory rate (RR) was held constant at 20 breaths/min. VE was measured as RR was set at 20, 30, 40, or 50 breaths/min while target PIP was held constant at 20 cm H2 O. Data were analyzed using the multiple regression technique. With the low compliance model, VE was nearly identical regardless of the ventilator setup. With the normal compliance model, minor differences in VE were observed, especially at the highest RR and PIP. VE was dependent on RR, PIP, and lung compliance. Overall, the ventilator setup resulted in minor changes in VE. Very high PIPs were required to deliver VE to the low compliance model. ETT size did not affect VE when lung compliance was low; however, smaller ETT size was a factor when test lung compliance was normal, decreasing delivered VE at higher PIP and RR. We conclude that with a Narkomed 2B adult circle system VE is dependent on PIP, RR, and lung compliance, but not on mode of ventilator setup. Implications: The results of this laboratory investigation indicate that when an adult circle system is used during infant anesthesia, the ventilation delivered depends primarily on the respiratory rate, peak inspiratory pressure, and the compliance of the lung being ventilated, rather than on the specific mode of ventilator setup. (Anesth Analg 1998;87:766-71)

Pressure-limited ventilation of infants with low-compliance lungs: the efficacy of an adult circle system versus two free-standing intensive care unit ventilator systems using an in vitro model.

UNLABELLED We compared the efficacy of a Drager Narkomed GS (North American Drager, Telford, PA) equipped with an adult circle system with two free-standing infant ventilator systems (Servo 300; Siemens Medical Systems, Danvers, MA and Babylog 8000; North American Drager) to deliver minute ventilation (VE) using pressure-limited ventilation to a test lung set to low compliance. To simulate a wide variety of potential patterns of ventilation, VE was measured at peak inspiratory pressures (PIP) of 20, 30, 40, and 50 cm H2O and at respiratory rates (RR) of 20, 30, 40, and 50 breaths/min. Each measurement was made three times; the average was used for data analysis using the multiple regression technique. Delivered V(E) was positively correlated with both PIP (P = 0.001) and RR (P = 0.001). Only minimal differences in VE were observed between the circle and the two free-standing systems. At lower RR and PIP, the Babylog 8000 system delivered slightly higher VE than the circle system, whereas at higher RR and PIP, the Babylog 8000 delivered slightly lower VE than the circle system; these differences in VE were not statistically significant (P = 0.45). The Servo 300 delivered slightly higher VE than the circle system in all test conditions, but these differences were not statistically significant (P = 0.09). None of the differences in delivered VE between the Servo 300 and the circle system are of clinical importance. IMPLICATIONS Our laboratory investigation suggests that pressure-limited ventilation delivered by a standard adult circle system compares favorably with that of freestanding infant ventilators used in pressure-limited mode. Changing from an adult circle system to a free-standing pressure-limited ventilator may not substantially improve ventilation of a low-compliance infant lung; the efficacy of such a practice should be investigated.

An adult system versus a Bain system: Comparative ability to deliver minute ventilation to an infant lung model with pressure-limited ventilation

UNLABELLED We compared the efficacy of an adult circle system versus a Bain system to deliver minute ventilation (V(E)) to an infant test lung model using pressure-limited ventilation. To simulate a wide variety of potential infant clinical states, V(E) was measured with two compliances: at peak inspiratory pressures (PIP) of 20, 30, 40, and 50 cm H2O and at respiratory rates (RR) of 20, 30, 40, and 50 breaths/min. Each measurement was made three times, and their average was used for analysis. Data were analyzed using the multiple regression technique. In both normal and low-compliance lung models, V(E) was nearly identical between adult circle and Bain systems (P = 0.67 for normal compliance model, P = 0.89 for low-compliance model). V(E) positively correlated with RR (P < 0.001), PIP (P < 0.001), and lung compliance (P < 0.001). Very high PIP or RR were required to deliver V(E) to the low-compliance lung model. The adult circle system is equivalent to the Bain system in its ability to ventilate an infant test lung over a wide range of RR, PIP, and two compliances during pressure-limited ventilation. V(E) is dependent of PIP, RR, and lung compliance. With low-compliance lungs, both systems require a high PIP. We conclude that both anesthetic systems deliver ventilation over a wide range of respiratory variables during pressure-limited ventilation in infants. IMPLICATIONS We obtained results from this infant test lung study that indicate that either an adult circle breathing system or the Bain system can reliably deliver ventilation over a wide range of respiratory variables during pressure-limited ventilation in infants.

FLUID WARMER AS A POTENTIAL SOURCE OF AIR BUBBLE EMBOLI

To the Editor:Recently, we provided anesthetic care for a 6-mo-old, 8-kg child during craniofacial reconstruction. Because of the 10 degrees head-up position used intraoperatively, a precordial Doppler probe was placed over the right atrium and checked for appropriate position by rapid infusion of i

A Comparison of Two Ventilator Systems Using an Infant Lung Model

STANDARD adult circle systems (with adult ventilator bellows and carbon dioxide absorber) equipped with pediatric circuit hoses, rather than semiclosed partial rebreathing systems or specially designed pediatric circle systems (with small ventilator bellows and carbon dioxide canister), often are used to ventilate infants and children during administration of anesthesia. If adult circle ventilator systems are used, it is important to understand the possible limitations and to make necessary modifications of adult techniques for use with infants. One limitation of this equipment for infant ventilation is the difficulty in determining how to set the tidal volume (‘IT) if using a time-cycled, volume-limited mode of ventilation to ensure that the patient receives the desired TV. The large compression volume of the circle

Anesthetic considerations for the pediatric plastic surgical patient

An understanding of the anesthesiologists concerns during pediatric plastic surgical procedures can facilitate the coordination of efforts between the multiple services involved in the care of these children. Prior to surgery, the childs history is obtained and physical examination is performed. The condition of the airway is the primary concern. Preoperative medication is usually given by oral routes to avoid injections. Induction intubation, maintenance, and emergence are discussed. Specific postanesthesia care is described. Special precautions are given for children having surgical repair of craniofacial anomalies. Cleft lip and palate and mandibular advancement are described.