Meperidine serum concentrations and analgesic response in postsurgical patients.

We examined the relationship between serum concentrations of meperidine hydrochloride and analgesic response in postsurgical patients allowed to use patient-controlled analgesia (PCA) and compared these findings with those of patients receiving conventional intramuscular (IM) dosing. Six patients who had undergone abdominal surgery were randomly assigned to receive postoperative analgesia with either PCA or IM therapy. A sequence of five-point pain and sedation scores and serum meperidine concentrations were obtained in all patients the day after surgery. Minimum effective concentration (MEC) was defined as that concentration of meperidine at which patients felt pain relief as indicated by a decrease in pain rankings. The mean MEC for patients using PCA, 296 +/- 112 ng/mL, was significantly lower than the mean MEC in patients receiving IM dosing (551 +/- 164 ng/mL, p less than 0.05). The mean maximum change in meperidine concentrations in the PCA group, 177 +/- 88 ng/mL, was significantly lower than that of the IM group (484 +/- 125 ng/mL, p less than 0.05). Mean maximum changes in pain and sedation scores for patients in the PCA group were not significantly different from those of the IM group. During this investigation patients using PCA experienced smaller swings in meperidine concentrations than did patients receiving IM injections. MEC analysis suggests that PCA patients may experience pain relief at lower meperidine concentrations than those needed by IM patients.

Relationship between values of bioelectrical impedance and creatinine clearance.

This investigation was conducted to determine if measurements of bioelectrical impedance in conjunction with serum creatinine concentrations are useful in predicting creatinine clearance. Twenty-eight healthy volunteers between 23 and 50 years of age followed an individualized protein diet to provide 1.2 g protein/kg/day for 3 consecutive days. At the beginning of day 3, a 24-hour urine collection was initiated. At the midpoint of urine collection, bioelectrical impedance measurements of resistance and reactance were taken, together with a single blood sample for assessment of serum creatinine concentration. Multiple linear regression techniques were used to identify significant values for predicting creatinine clearance. Resistance and serum creatinine concentration were identified as significant predictors. The measured creatinine clearance was compared to that predicted by the impedance-derived model that we developed, as well as other established estimation methods. Mean absolute prediction errors in creatinine clearance using this model were significantly lower than those obtained using four empiric methods. Bioelectrical impedance may provide a noninvasive, quick, and accurate method for predicting creatinine clearance from serum creatinine concentration values.

Developing and implementing standards of practice for clinical pharmacy services.

The authors' department has attempted to bring more order to the provision and evaluation of clinical services through the development of "Clinical Standards of Practice." A pilot project was initially conducted on one satellite. Pharmacists were asked to prepare a list of minimum standards that could be agreed upon and that everyone believed were achievable even on the busiest days. After standards were developed and implemented, a procedure was established to evaluate compliance through review of pharmacy records and patient materials. Staff received feedback concerning the results of the review. As a result of the success with the pilot, Clinical Standards of Practice have been developed by staff and are in use throughout the department. Plans for the future include continuous revision of the standards to reflect changing departmental goals and directions and a change to a "pharmacist specific" rather than a current "nursing unit specific" monthly review format to facilitate performance review and staff development. Eleven standards are shown in the appendices.

Minimum urine collection periods for accurate determination of creatinine clearance in critically ill patients.

The accuracy of creatinine clearance (CLcr) determinations obtained from urine collections of less than 24 hours duration and the cyclical variation in creatinine excretion were studied in 10 critically ill patients with trauma or postoperative complications. Data from patients who received drugs or had diseases known to influence creatinine production or interfere with assay methods were excluded. Twelve consecutive two-hour urine collections and midpoint blood samples were obtained for each patient. Urine and serum samples were assayed for creatinine content by kinetic and enzymatic methods, respectively. The mean 24-hour CLcr was 110.6 +/- 47.0 mL/min. Clearance values determined from 8- and 12-hour collections were within 20% of the 24-hour CLcr value, and values determined from 14- to 22-hour collections were not significantly different from the 24-hour CLcr value. Mean differences between each 2-hour interval and the 24-hour interval were not significant for the 12 collection intervals. In critically ill trauma or postsurgical patients, the 24-hour CLcr can be estimated from an 8-hour urine collection if a deviation of up to 20% from the 24-hour value is clinically acceptable. No significant cyclical variation in creatinine excretion over 24 hours was found.

Patient-controlled analgesia in the terminally ill cancer patient.

Patient-controlled analgesia (PCA) is a relatively new therapeutic modality which has allowed postsurgical patients to safely and effectively self-administer doses of intravenous narcotics via a syringe pump and sequencing device. A pilot study was designed to evaluate PCA's safety and effectiveness in the terminally ill cancer patient. Eight patients whose chronic pain was not adequately controlled by oral narcotics were permitted to use PCA for a minimum of 48 hours. Respiratory rates, sedation rankings, and pain rankings indicated these patients achieved satisfactory analgesia with a minimum of sedation and experienced no respiratory depression. Three patients were switched to oral regimens using PCA dosing as a guide. Pain and sedation rankings were similar to those registered while exclusively on PCA. This self-dosing technique was judged to be safe, effective, and able to accommodate wide fluctuations in analgesic need when treating pain in the terminally ill cancer patient. The results obtained in these patients support further trials using PCA to individualize oral analgesic regimens.

Specific 125I radioimmunoassay for morphine.

In this specific radioimmunoassay procedure for morphine, samples are first subjected to an extraction procedure to remove the major metabolite of morphine (morphine-3-glucuronide), then quantified by use of a commercial radioimmunoassay kit with 125I-labeled morphine. Concentrations between 10 and and 100 micrograms/L are routinely measured with a within-run CV of less than 2.0% and a between-run CV of 3.5%. This rapid, specific, and sensitive method requires minimal technical skills and analytical equipment that is common to most laboratories.

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.

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.

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.