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Biomedical subjects

D A Graves

Publications and source records attributed to D A Graves.

36 records · Page 2Linked to original sources

Patient-controlled analgesia.

Patient-controlled analgesia is a relatively new and investigational technique that permits patients to treat pain by directly activating doses of intravenous narcotics. The technique was developed in response to the undertreatment of pain in hospitalized patients. Continuous narcotic infusion and intraspinal narcotic administrations also have the potential to provide continuous, uninterrupted analgesia, but do not allow simple dose attentuation to avoid overdosage. Patient-controlled analgesia is used to treat postoperative and labor pain and pain associated with terminal illness; it delivers analgesic more effectively with fewer side effects than conventional parenteral narcotic therapies. The technique is also an ideal investigative instrument for studying equianalgesic states. Several foreign-made devices are now being used under investigational sanctions in this country, and it is anticipated that several American manufacturers will be seeking regulatory approval to market the devices.

Administration, Oral↗

Corneal splitting in the developing lamprey Petromyzon marinus L. eye.

The cornea of the adult lamprey has both dermal (spectacle) and scleral components. These are separated by a thin mucoid layer that allows free movement of the globe. This study has shown that during the larval (ammocoete) stage, the lamprey cornea develops in a manner similar to that of other lower vertebrates. Just prior to the period of transformation to the adult parasite, the outer dermal portion of the ammocoete cornea (spectacle) consists of an anterior stratified columnar epithelium with goblet cells at the surface. The stroma of the dermal cornea consists of a thick outer layer of orthogonally oriented collagen with branching fibroblasts and a thin, loosely organized inner layer with slender elongated fibroblasts. The scleral cornea is lined internally by a flattened monolayer of mesodermal cells, the corneal endothelium. Its narrow stroma is composed entirely of thin, orthogonally arranged, collagen-fiber lamellae, and is bounded externally by a thin continuous mesothelial layer of cells that abuts directly onto the loose stromal component of the dermal cornea. During the early stages of transformation, the anterior epithelium of the dermal cornea becomes stratified squamous in type. Later, the inner loose stroma of the dermal cornea (spectacle) begins to separate from the scleral cornea components, and a third complete mesothelial layer forms a distinct inner border for the dermal cornea. A mucoid layer is formed between the dermal (spectacle) and scleral corneas and remains throughout the adult life.

Animals↗

Patient-controlled analgesia: a new concept of postoperative pain relief.

This report concerns evaluation of patient-controlled analgesia (PCA) in the form of two preliminary investigations. In the first study, the patient-controlled analgesia device, which consists of a pump linked to a timer so that patients can activate intravenous administration of morphine sulfate to themselves during the postoperative period, was used in seven morbidly obese patients. The amount of morphine used during the first 36 hours was found to vary between 32 and 185 mg, with a significant difference in drug usage when related to weight as well as to body surface area. In the second study, morbidly obese patients undergoing gastric bypass operations were prospectively randomized into 12 patients who used the PCA device in the postoperative period and 12 patients who were given standard intramuscular dosages of morphine sulfate. An analgesia and sedation scale was then used to compare the two groups. The patients in the PCA group were able to maintain a state of adequate analgesia without sleep with a significantly greater frequency than were those in the intramuscular injection group. On the basis of answers to a questionnaire given to the patient after 60 hours of morphine analgesia, it was apparent that the PCA group was much more satisfied with that form of postoperative analgesia. It would appear that PCA is an efficacious and safe method of providing for postoperative pain relief.

Analgesia↗

Pseudoephedrine absorption from controlled release formulations: absorption rate constant estimation methods.

Five methods of absorption rate (Ka) estimation were compared using data from a previously reported bioavailability study: Wagner-Nelson (WN), asymptotic WN (AWN), the Hendeles-Weinberger modification of the WN (HW), nonlinear regression performed on plasma concentration vs time data with fixed elimination rates (NL), and nonlinear regression performed on the cumulative sum of AUCs obtained during WN analysis (AUCNL). The maximum plasma concentration (Cmax) and the time at which Cmax occurred (Tmax) were predicted with each method's respective Ka's, and these were compared to observed values. The WN and HW were consistently biased in their predictions of Cmax and Tmax, providing slower Ka's than any of the other methods. AWN could only be used for the reference treatment. Both NL and AUCNL provided unbiased estimations, but AUCNL had a high level of imprecision. With this set of data, only NL was an acceptable method for accurately estimating Ka.

Adult↗

Influence of a standard meal on the absorption of a controlled release pseudoephedrine suspension.

The influence of a standard meal on the extent and rate of absorption of pseudoephedrine from a liquid controlled release (CR) formulation (Pennkinetic System) was studied in 16 normal male volunteers. Equivalent single doses of an immediate release reference syrup (IR-Sudafed) and the CR suspension were each studied under both fasted and postprandial conditions. AUC results showed no significant influence of food or formulation, indicating that the CR formulation was absorbed to the same extent as the IR product under all conditions. CMAX and TMAX tabulations under fasted conditions indicated that the CR preparation peaked at a lower level at a later time. Food diminished IR CMAXs but the CR suspension's CMAXs and TMAXs were apparently unaffected by food. This study indicates that this CR pseudoephedrine suspension releases drug independently of food intake.

Adolescent↗

Variation in postoperative analgesic requirements in the morbidly obese following gastric bypass surgery.

Patient-controlled analgesia is a relatively new method of administering intravenous narcotics for postoperative pain relief. The technique involves the self-administration of a given analgesic in a bolus dose with the aid of a timed infusion and sequencing device. Ten morbidity obese patients undergoing elective gastric bypass surgery were treated in a prospective, unblinded, pilot project to evaluate the efficacy of patient-controlled analgesia. Analgesic therapy was satisfactory in all patients. The mean total dose of morphine sulfate administered during the first 36 hours postoperatively was 66 mg, an average of 1.7 mg/hr. There was a tenfold variation (17.5-175 mg) in the 36 hr total dose. The total dose was not related to body surface area, age, sex, dose per injection, or anesthetic agent. The large variation in individual narcotic analgesic requirements could be a major factor in the suboptimal management of postoperative pain with conventional dosing. Patient-controlled analgesia may circumvent these problems.

Adult↗

Extraordinary analgesic requirement in a patient previously unexposed to narcotics.

Patient-controlled analgesia (PCA) is a relatively new therapeutic modality that allows patients to administer doses of intravenous narcotics, using a syringe pump and sequencing device. We used PCA to deliver analgesic therapy to a 35-year-old man seriously injured in an aviation accident. Although the patient gave no previous history of narcotic use or abuse, he required morphine dosing rates as high as 56 mg/h to maintain adequate analgesia. The delivery of relatively high doses of narcotic was not accompanied by significant sedation, as might be expected. The patient underwent two surgical procedures while on PCA therapy. Following each procedure, dosing requirements increased, but within three days after each operation, dosing tapered. The patient was converted to oral hydromorphone therapy, which gradually was tapered and then discontinued. PCA should be considered a useful therapeutic adjunct in the management of patients refractive to empirical narcotic analgesic regimens.

Adult↗

Relationship between plasma morphine concentrations and pharmacologic effects in postoperative patients using patient-controlled analgesia.

In postoperative patients using patient-controlled analgesia (PCA) to administer i.v. doses of morphine sulfate, respiratory rates and subjective rankings of pain, sedation, and liking for the drug were correlated with plasma morphine concentrations. In 12 patients selected before surgery, the initial morphine sulfate dose of 0.6 mg/sq m was increased or decreased as needed. Every two hours, cumulative morphine sulfate dose, respiratory rate, and sedation were recorded by the nurse, along with the patient's evaluation of pain and liking for the drug. Plasma was collected in the morning and evening during PCA therapy for morphine analysis. Data were analyzed by analysis of covariance. Dosing rates and rankings of pain, sedation, and liking decreased as a function of time postoperatively, but respiratory rates did not. Sedation and respiratory rates were independent of morphine concentration. Liking of the drug increased directly with plasma morphine concentration but decreased with time. A high level of pain was directly related to morphine use. For all significant relationships, there was high interpatient variability, with the exception of changes in pain rankings induced by morphine. Patients defined a minimum effective plasma morphine concentration of 20-40 ng/mL. The maximum plasma morphine concentration achieved by self-administration was 82 ng/mL. These postoperative patients used patient-controlled analgesia to deliver morphine sulfate i.v. for pain relief, not for euphoria, and did not exhibit sedation or respiratory depression. Morphine was consistently effective at plasma concentrations of 40 ng/mL or greater.

Adult↗

Bioavailability assessment of a new liquid controlled-release pseudoephedrine product.

Development of a liquid controlled-release pseudoephedrine product is described. Two bioequivalence studies were conducted. In a single-dose study involving 20 subjects, the bioavailabilities of five controlled-release suspensions with a broad range of drug-release rates were compared with an immediate-release form of pseudoephedrine hydrochloride in a four-way crossover, incomplete block, sequence-randomized study. Serial blood sampling up to 36 hours after drug ingestion provided area-under-the-curve (AUC), maximum plasma concentration (Cmax), and time to peak (tmax). In the multiple-dose study, involving 18 subjects, the bioavailability of the optimal formulation determined from the single-dose study was compared with a reference pseudoephedrine hydrochloride syrup. Serial blood sampling up to 12 hours after drug ingestion was performed to determine AUC, Cmax, and tmax. The single-dose investigation showed that all formulations were bioequivalent except the product with the slowest release rate, which had lower AUC and Cmax values. The results of the multiple-dose study confirmed these findings with the reference syrup. The use of a series of drug formulations with a wide range of release rates permitted selection of an optimal product in addition to providing the information needed to ensure continuous production of bioequivalent products.

Adolescent↗

Morphine requirements using patient-controlled analgesia: influence of diurnal variation and morbid obesity.

The influence of diurnal variation and morbid obesity on the morphine requirements of patients using patient-controlled analgesia (PCA) was studied. Forty-six patients undergoing either elective (Group I) or gastric bypass (Group II) surgery composed the study group. Patients were allowed to use the PCA machine for 36 to 72 hours postoperatively to deliver 0.6 mg/sq m doses of morphine sulfate intravenously. Counters on the device indicating the number of doses received were monitored every two hours along with vital signs and a pain and sedation rating. Dosing rates were studied with regard to the time of day. Morbid obesity had no significant effect on dosing rate requirements. Analyses revealed a significant diurnal rhythm in morphine dosing rate requirements despite a 27-fold interpatient variability. Peak analgesic use was at 0900, and the nadir was at 0300. Patient pain rankings did not indicate any changes in pain status, demonstrating PCA's use of analgesia as an endpoint for dosing. Sedation status showed a higher degree of sedation at night when compared with the daytime values, documenting that sedation was not drug-induced. There is a circadian variation in narcotic analgesic need in the postoperative patient that is met appropriately by PCA.

Adult↗