Analysis of pain management in critically ill patients.

We analyzed the adequacy of pain control for 17 trauma patients during the initial part of their stay in the intensive care unit, and assessed reasons for inadequate analgesia, if it occurred. Patients, and physicians, and nurses were interviewed. A verbal pain intensity scale was used to determine whether patients received adequate analgesia. Patients were asked if the pain hindered their activities, and whether they requested pain medication from their caregivers. Caregivers were questioned whether patients received adequate analgesia. Prescribed morphine regimens and the amount of narcotic administered were analyzed. Twenty-seven percent of patients rated pain intensity as moderate and 47% as severe. Ninety-five percent of housestaff and 81% of nurses reported the patients received adequate pain control. Forty-seven percent of the patients who had moderate or severe pain asked their physician for more pain medication, and 65% asked the nurse. Thirteen residents did not order a larger dose of morphine due to concern about respiratory depression or hypotension. Morphine dosages ranged from 1-8 mg intravenously every 1-2 hours as necessary. Nurses administered less than the maximum amount ordered 58% of the time. The mean dosing interval was 2.3 hours. Barriers to adequate pain management were disparity in the perception of pain between patients and caregivers; patients not requesting more analgesia despite despite the presence of moderate to severe pain; and physician and nurse concerns about patients' adverse physiologic response to increased dosages.

Current patterns of prescribing and administering morphine in trauma patients.

We attempted to characterize the current prescribing practices and administration patterns for intravenous intermittent morphine in trauma patients in a multicenter, open prospective, observational study. The subjects were 141 patients admitted to the surgical intensive care units (ICU) of five United States trauma centers within 12 hours of injury who received intermittent intravenous morphine for pain relief. The study was conducted from April 15, 1992, to February 15, 1993. Data obtained during the first 32 hours of the ICU stay included morphine regimen, doses administered, and time between doses. One hundred sixty-one orders were prescribed by surgeons. The most frequently ordered dose was 2-4 mg and the most frequently ordered interval was every hour as necessary. There was no relationship between the severity of injury and the minimum dose ordered. During the 492 nursing shifts studied, 1257 doses were administered. Of these, 44% were at or below the minimum amount prescribed by the surgeons. Thirty-three percent of the patients received a dose at an interval of more than 3 hours. We concluded that small amounts of narcotic analgesics are given to severely injured patients, and amount ordered is not affected by the severity of injury.

Effect of analgesic treatment on the physiological consequences of acute pain.

Physiological responses to acute pain are described, and the effects of different analgesic techniques on these responses are discussed. The body's response to acute pain can cause adverse physiological effects. Pain can impede the return of normal pulmonary function, modify certain aspects of the stress response to injury, and alter hemodynamic values and cardiovascular function. It can produce immobility and contribute to thromboembolic complications. In addition, pain can slow a patient's recovery from surgery and contribute to increased morbidity. Fewer pulmonary complications occur when adequate analgesia is provided through the use of epidural narcotics and local anesthetics, particularly if the injury or surgery involves the lower part of the body. Continuous morphine infusions, intercostal nerve blocks, and transcutaneous electrical stimulation do not alter the frequency of pulmonary complications. The effectiveness of patient-controlled analgesia in reducing postoperative pulmonary complications is still not known. Epidural local anesthetic therapy inhibits the stress response, particularly in operations involving the lower abdomen or extremities; this technique is less effective during major abdominal procedures. Suppression of endocrine-metabolic changes following lower abdominal surgery requires neural block to the fourth thoracic segment. Epidural narcotics partially inhibit the stress response after lower abdominal or extremity surgery but not after upper abdominal or thoracic surgery. Local anesthetics applied to the surgical site, intercostal nerve blocks, and intrapleural and intraperitoneal administration also do not modify the stress response. Adequate analgesia through the use of local anesthetics and narcotics postoperatively generally results in improved cardiovascular function, decreased pulmonary morbidity and mortality, earlier ambulation, and decreased likelihood of deep vein thrombosis. Some data suggest that improved patient outcome occurs with adequate analgesia. Block of afferent and efferent neural pathways by local anesthetics seems to be the most effective analgesic modality in lessening the physiologic response to pain and injury.

Identification of patient-controlled analgesia overdoses in hospitalized patients: a computerized method of monitoring adverse events.

OBJECTIVE: To describe and validate a computer-based quality assurance method that detects narcotic overdoses associated with patient-controlled analgesia (PCA) use. SETTING: Two acute care teaching hospitals. PATIENTS: 4669 patients who received PCA. INTERVENTIONS: The following patient lists were obtained during a two-year period from both hospital information systems: those who received PCA and (1) received naloxone, a narcotic antagonist, (2) were transferred to an intensive care unit, (3) had a cardiac or respiratory arrest, or (4) died. Possible overdoses were defined as patients who appeared on the PCA list and one of the other lists. Charts were reviewed if the patient's name appeared on the PCA and one of the other lists. Patients were judged to have experienced a narcotic overdose if there was an immediate improvement in blood pressure, respiratory rate, or mental status after the administration of naloxone. RESULTS: The search strategy identified 294 possible overdoses in 1499 patients who received PCA. Ten charts were unavailable for review. An actual overdose occurred in 11 patients. The accuracy of the new method was compared with that of the hospitals' present reporting methods. Eleven overdoses were identified by the computer search, but only 6 overdoses were identified in incident and adverse drug reaction reports. CONCLUSIONS: The systematic computer search identified almost twice as many adverse incidents than were reported by the traditional hospital methods.

Difficulties in diagnosing narcotic overdoses in hospitalized patients.

OBJECTIVE: To describe the clinical presentation of narcotic overdose in hospitalized patients and to differentiate this circumstance from other conditions often misdiagnosed as overdose. DESIGN: Case series. SETTING: Two acute-care teaching hospitals. PATIENTS: Forty-three hospitalized patients who received naloxone for a clinically suspected narcotic overdose. INTERVENTIONS: Two investigators independently evaluated each incident to determine whether the patient had a narcotic overdose. The patients were judged to have had an overdose if caregivers documented an immediate improvement in mental status, respiratory rate, or blood pressure after naloxone administration. MEASUREMENTS: The clinical presentation of a narcotic overdose in hospitalized patients was defined. Conditions misdiagnosed as an overdose were determined. MAIN RESULTS: Symptoms improved rapidly with the administration of naloxone in 28 incidents (65 percent) and were designated overdose. In 15 other instances there was no improvement in symptoms; these patients were designated nonoverdose. Only half of the overdose patients had a respiratory rate < 8 breaths/min immediately prior to naloxone administration. Only two of the overdose patients had the classic triad of symptoms (respiratory depression, coma, and pinpoint pupils). Other overdose patients had only one or two of the classic signs. The clinical presentation of narcotic overdoses in hospitalized patients did not include respiratory depression, hypotension, or coma in the majority of patients. All overdose patients showed a decrease in mental status. The majority of nonoverdose patients had pulmonary conditions that were misdiagnosed as a narcotic overdose. CONCLUSIONS: Narcotic overdoses in hospitalized patients seldom fit the classic description. The lack of respiratory depression does not mean the absence of a narcotic overdose. Patients who receive narcotics and develop a significant decrease in mental status should be evaluated for a possible overdose. Pulmonary, neurologic, cardiovascular, and electrolyte abnormalities often are misdiagnosed as a narcotic overdose in hospitalized patients.

Pharmacokinetic evaluation of a new oral cyclosporine formulation.

STUDY OBJECTIVE: To compare the pharmacokinetics of a new oral cyclosporine preparation with those of cyclosporine solution diluted in Isocal and the intravenous formulation. DESIGN: Randomized, crossover trial. SETTING: Tertiary care referral center. PATIENTS: Seven pediatric liver transplant recipients who were receiving oral cyclosporine as part of their immunosuppressive regimen. All patients completed the study. INTERVENTIONS: Pharmacokinetic studies were performed with the intravenous and oral dosage forms. Patients received one dose of intravenous cyclosporine, and then were randomized to receive their usual oral cyclosporine dose incorporated into a chocolate wafer or mixed with Isocal. After a minimum of 3 days, the alternative preparation was administered. Serial cyclosporine blood samples were collected at predetermined intervals for 12 hours after the third dose for each regimen. Concentrations were determined by high-performance liquid chromatography. The data for the three dosage forms were fit simultaneously with a two-compartment model. MEASUREMENTS AND MAIN RESULTS: No difference was seen in F, ka, Cmax, and tmax between the two oral cyclosporine preparations (p > 0.05). No new rejection episodes occurred during the study period. CONCLUSIONS: We conclude there is no difference in the bioavailability of the oral solution and the chocolate formulation. We believe the new preparation may increase patient compliance and ensure administration of a complete dose compared with the currently marketed solution.

Glucose response to abrupt initiation and discontinuation of total parenteral nutrition.

Plasma glucose was studied during the initiation of total parenteral nutrition (TPN) and the discontinuation of TPN without a tapering schedule. Blood was sampled every 5 minutes for 2 hours after the start of TPN and 1 week later as TPN was discontinued. A total of 14 initiations and 14 discontinuations were studied in 18 patients. Severity of illness in patients ranged from stable condition postoperatively to multiple-system failure; six patients had diabetes mellitus. The TPN solution was a 3:1 admixture that provided a caloric intake equal to 1.2 times the resting energy expenditure, with 40% fat and 60% carbohydrate calories. An average of 1963 kcal was provided per day (340 g of glucose, 79 g of fat). During the initiation phase, the mean increase in plasma glucose was 60 mg/dL. The increase for diabetic patients was 79 +/- 14 mg/dL compared with 52 +/- 23 mg/dL for the nondiabetics. During the discontinuation phase, the mean plasma glucose decreased 40 +/- 20 mg/dL; two patients with high concentrations of regular insulin (50 and 100 units) showed an increase in plasma glucose when the TPN was stopped. Plasma glucose returned to the preinfusion baseline after discontinuation. During both initiation and discontinuation, plasma glucose showed little change after the first 60 minutes. No clinical symptoms of hypoglycemia were observed. In conclusion, TPN as a 3:1 admixture can be safely started as full nutrition support and stopped abruptly without a tapering schedule. Plasma glucose response is rapid, predictable, and mostly complete within 60 minutes.

Narcotic use in the hospital: reasonably safe?

OBJECTIVE: To determine the causes and frequency of overdoses associated with the administration of opioid analgesics in hospitalized patients. DESIGN: Case series. SETTING: Two acute care teaching hospitals. PATIENTS: Eighty-one hospitalized patients who received naloxone for a clinically suspected narcotic overdose. INTERVENTIONS: Three investigators reviewed each patient who received naloxone during a 12-month period. The patients were judged to have a narcotic overdose if caregivers documented an immediate improvement in mental status, respiratory rate, or blood pressure after naloxone administration. MAIN OUTCOME MEASURES: The number and causes of narcotic overdoses were determined. The frequency of morphine and meperidine overdoses was calculated. The number of incidents reported using incident or adverse drug reaction reports or the appropriate International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code. RESULTS: In the 22 overdoses that occurred, 14 (64 percent) were caused by medication prescribing, compounding, or administration errors and potentially were preventable. The remaining eight patients experienced an overdose despite receiving appropriate amounts of opioids. The frequency of overdoses was 0.4 and 0.2 percent of total patients receiving morphine or meperidine, respectively, at the two hospitals. Nonreporting of these narcotic overdoses was frequent. In one hospital, 1 incident report and 3 adverse drug reactions were reported for 17 overdoses. At the second hospital, 1 incident report and 1 adverse drug reaction were reported for 6 overdoses. None of the patient charts included an ICD-9-CM code that documented the problem. CONCLUSIONS: The causes of overdoses are not limited to prescribing and administration errors. Some patients, despite proper execution of appropriate orders, develop a narcotic overdose. Caregivers must be aware of this problem and monitor patients for a decrease in mental status and respiratory rate. In addition, we conclude that an important number of hospitalized patients develop an overdose even though the frequency is low related to the number of patients receiving narcotics.

Effect of individualized pharmacokinetic dosing on patient outcome.

OBJECTIVE: To study the effect of individualized pharmacokinetic dosing of aminoglycosides on patient outcome. DESIGN: Prospective, randomized study. SETTING: Tertiary care hospital. PATIENTS: Ninety-five patients with documented Gram-negative infections received 97 courses of aminoglycoside therapy. INTERVENTIONS: Patients were randomized between pharmacokinetic dose adjustment and monitoring or traditional physician-directed techniques. Patients were stratified by severity of underlying illness before randomization. MEASUREMENT AND MAIN RESULTS: Sixty-two courses of treatment were satisfactorily completed. Patients in the severely ill group (eight kinetic, eight traditional) had significantly (p less than .05) better survival (7 kinetic, 3 traditional) when managed with pharmacokinetic consultation. The kinetic arm received greater doses (156 +/- 59 mg/dose; 2.4 +/- 0.6 mg/kg) than the traditional arm (81 +/- 27 mg/dose; 1.5 +/- 0.6 mg/kg) (p less than .001). In addition, the dose per day (mg/kg) was greater in the kinetic arm (4.1 +/- 1.5) than the traditional arm (3.2 +/- 1.3) (p less than .001). The improved survival was achieved by attaining therapeutic peak serum concentrations earlier in the course of the infection and by administering more total aminoglycoside without increasing toxicity. CONCLUSIONS: We conclude that pharmacokinetic management of aminoglycoside dosing may improve the outcome of severely ill patients.