Evaluation of cyclooxygenase 2 inhibitor use in patients admitted to a large teaching hospital.

BACKGROUND: The heavy usage of coxibs in Australia far outstrips the predicted usage that was based on the treatment of patients with risk factors for upper gastro-intestinal adverse events from conventional anti-inflammatory agents. This raises questions regarding the appropriateness of prescribing. AIMS: To determine: (i) the relationship between prescriptions for cyclooxygenase 2 (COX-2) inhibitors and objective evidence of inflammatory arthritis, (ii) prior experience with paracetamol and/or conventional non-steroidal anti-inflammatory drugs (NSAIDs), and (iii) contraindications to the use of NSAIDs. METHODS: Drug utilization evaluation and rheumatological assessment was conducted on 70 consecutive patients admitted on COX-2 inhibitors to a 480-bed metropolitan hospital. The main outcome measures were: the indication for COX-2 inhibitor; objective evidence of inflammatory arthritis; previous trial of paracetamol or conventional NSAIDs; and patient satisfaction. RESULTS: Only 11 patients (16%) had symptoms or signs of an inflammatory arthropathy, and met Pharmaceutical Benefits Schedule criteria for prescribing a COX-2 inhibitor. Fifty-nine patients (84%) had chronic osteoarthritis, degenerative spinal disease, injury or malignancy, without overt active inflammation. Fourteen patients (20%) had trialled regular paracetamol prior to using any NSAID treatment. Conventional NSAIDs had been previously used by 51 patients (73%). Eleven patients (16%) reported previous adverse gastrointestinal effects from conventional NSAIDs. On the basis of significant renal impairment (creatinine clearance <50 mL/min) or cardiac failure, cautions or contraindications applied to the use of any form of NSAID in 49% of patients. Fifteen patients (21%) had demonstrable worsening of their renal function after commencement of a COX-2 inhibitor. Thirty-one percent of patients considered the drug was effective (rated >5/10). CONCLUSIONS: Drug utilization data indicate that COX-2 inhibitors are frequently used first line for degenerative osteoarthritis in the absence of overt inflammation, without prior adequate trial of paracetamol and with disregard for the cautions and contraindications of these agents. These findings may explain the unprecedented Pharmaceutical Benefits Schedule expenditure on COX-2 inhibitors in Australia.

Evaluation of dosage adjustment in patients with renal impairment.

AIMS: To determine whether appropriate dosage adjustments are made in patients with significant renal impairment for drugs with a high fractional renal clearance. METHODS: Evaluation of dosage adjustment was performed in patients who were admitted to a 480-bed metropolitan hospital (Princess Alexandra Hospital, Brisbane, Australia) with an estimated creatinine clearance of < or =40 mL/min. All drugs had a high fractional renal excretion. A prescribed dose within 30% of the calculated dose was considered appropriate. RESULTS: Doses were found to be inappropriately high in 111 (44.8%) of 248 admission prescriptions of the targeted drugs. Doses were appropriately reduced in hospital in 26 patients (23.4%). Seventy-three (29.3%) prescriptions were continued with excessive doses. Only 34 prescriptions for the target drugs were initiated in hospital, of which 88.2% were appropriately dosed. CONCLUSIONS: A significant percentage of patients with renal impairment are admitted to hospital on inappropriately high doses of drugs, with a high fractional renal excretion and low therapeutic index. Doses are appropriately reduced in hospital in some patients but there is still room for improvement [corrected].

Alveolar and peripheral venous gas changes during breath-hold diving.

Two fit young men were tested in a laboratory pool at 22 degrees C and 1 m depth before and after hyperventilation/breath-hold diving lasting 90 seconds. The percentages of alveolar oxygen and carbon dioxide were determined on a Polygas analyser and converted to partial pressures (PAO2 and PACO2) at an atmospheric pressure of 86 kPa at 20 degrees C, room temperature. PAO2 and PACO2 values were cross-checked by collecting expiratory gas in a Douglas bag and using the Haldane gas analyser. Peripheral venous blood was 'arterialized' and analysed for CO2 (PVCO2) using the Radiometer ABL1 gas analyser. For ethical reasons, arterial punctures were not considered in these healthy subjects. Peripheral venous blood was obtained under near steady-state conditions from the dorsum of the hand, which was warmed to 38 degrees C. The results of hyperventilation/breath-hold diving are illustrated. PAO2 increased after hyperventilation and decreased to below 5 kPa after the dive. PACO2 decreased after hyperventilation and increased after the dive. PVCO2 decreased after hyperventilation and increased after the dive. All values approached a common point between 3 and 5 kPa after the 90-second dive. The CO2 content of arterialized peripheral venous blood closely follows that of alveolar air.

Decompression sickness in South African sport divers.

During the period 1 January 1969 to 31 December 1977 56 underwater diving accidents were reported among amateur sport divers in South Africa. Of these, 4 were diagnosed and treated as decompression sickness (DS), an incidence of 7%. Analysis of the 4 cases of DS indicates that they were all in the serious type II neurological category. This is in keeping with results found in Hawaii and Australia, and the reasons for this finding are discussed. An emergency medical system (EMS) for on-site, pre-chamber and decompression chamber treatment is discussed.

South African underwater diving accidents, 1969-1976.

Since 1969 a survey of diving accidents involving South African amateur divers was undertaken. The South African Underwater Union diving accident report form was used, and various State agents (SA Police and inquest courts) and individual divers and club instructors were questioned. This survey covers the period up to the end of June 1976. Data acquired during the 8-year period 1969 - 1976 are compared. A conservative estimate from the number of certificates issued to club divers indicates a 25% increase in diver population, while the number of fatilities has decreased from 0,1% in 1971 to 0,016% in 1976, indicating the importance of accident reporting in determining safety trends. In general, a change in pattern is observed during the last 4 years, showing more SCUBA than breath-hold fatalities. The formation of the Decompression Sickness and Diving Accidents Investigation Panel as a further measure to decrease fatal diving accidents is discussed.

Bradycardia during human diving.

The bradycardial response to the diving reflex, which occurs in man and in diving animals, is thought to be a physiologically protective oxygen-conserving mechanism whereby the animal is kept alive during submergence. The physiology and nervous pathways are not yet fully understood, but several investigators have pointed out the potentially fatal outcome of an accentuated diving reflex. the CO2 content of the peripheral venous blood has been proved variable and unpredictable during the hyperventilation-breath-hold dive cycle in man. A group of 8 male divers (average age 34 years) was investigated during breathhold dives to 3,3 m in a swimming pool. Heart rates were recorded and compared at various stages during breath-hold and SCUBA (self-contained underwater breathing apparatus) dives, viz. when resting on the surface, breath-holding, hyperventilating and swimming underwater. Two divers performed extreme breathhold endurance tests lasting 135 seconds underwater. All divers had a tachycardia after hyperventilation and a bradycardia after breathhold diving, lasting 80-100 seconds. Extrasystoles were recorded during some of the breathhold dives. Prolonged submergence caused extreme bradycardia (24/min) with central cyanosis. Bradycardia during diving may be a physiological )2-conserving reflex or the start of a pathophysiological asphyxial response.