A randomized, double-blind evaluation of ketorolac tromethamine for postoperative analgesia in ambulatory surgery patients.

BACKGROUND: Given the trend toward early discharge of patients after surgery and the inherent adverse effects of opioid analgesics, we compared a new nonsteroidal antiinflammatory drug, ketorolac tromethamine, given intravenously (iv) and then orally, with two commonly prescribed opioid analgesics in ambulatory patients for up to 1 week after surgery. METHODS: In this study incorporating a double-blind, multi-dose design, 221 patients who had moderate or severe pain after surgery were randomized to one of three treatment groups: group K30 received 30 mg iv ketorolac twice, then 10 mg iv every 30 min as required to control pain, up to six doses, followed by 10 mg oral ketorolac every 4-6 h; group F50 received 50 micrograms iv fentanyl at the same time intervals as in group K30, followed by 60 mg codeine plus 600 mg acetaminophen (C+A) orally every 4-6 h; and group F10 received the same combination as did group F50, but only 10 micrograms fentanyl per dose. RESULTS: Compared with 50 micrograms fentanyl iv, 30 mg iv ketorolac provided delayed but otherwise equivalent analgesic effects and was associated with similar side effects. Compared with C+A, 10 mg oral ketorolac was associated with a lower incidence of nausea and somnolence and earlier return of bowel function but not better pain relief, drug tolerability, quality of life, or psychologic well-being. CONCLUSIONS: Ketorolac, when used in an iv and then oral sequence, is a safe and effective analgesic in the ambulatory surgery setting. It has a slower onset than fentanyl, but causes fewer side effects than C+A.

Comparison of intravenous ketorolac tromethamine and morphine sulfate in the treatment of postoperative pain.

This study compared the efficacy and safety of ketorolac tromethamine and morphine sulfate in alleviating moderate or severe pain immediately after major surgery. One hundred twenty-two patients were randomly assigned to receive single intravenous injections of ketorolac 10 mg, ketorolac 30 mg, morphine 2 mg, or morphine 4 mg; patients could receive a second dose 15 minutes thereafter, upon request, and most received both available doses. Analgesic efficacy was measured by interviewing patients and assessing pain intensity and pain relief for 6 hours after the first medication administration. The two drugs showed a similar onset of action, peaking 1 hour after administration. When placed in order of descending efficacy, the mean scores for most efficacy measures fell into the following sequence: ketorolac 30 mg, ketorolac 10 mg, morphine 4 mg, and morphine 2 mg. There were no statistically significant differences among the two ketorolac doses and the high dose of morphine, but all three of these treatments were significantly superior to the low morphine dose. One patient who took morphine 4 mg withdrew because of drowsiness; other common adverse events reported included nausea, vomiting, somnolence, and dyspepsia. There were no statistically significant differences in the frequency of adverse events among the treatment groups. Intravenous ketorolac is effective for the treatment of postoperative pain.

Analgesic efficacy and safety of single-dose oral and intramuscular ketorolac tromethamine for postoperative pain.

The efficacy and safety of the analgesic drug ketorolac tromethamine in the treatment of moderate to very severe postoperative pain was assessed in five dose-ranging studies with single-dose, double-blind, randomized, parallel-group designs. The drug was administered orally (2.5-200 mg, 352 patients in three trials) and intramuscularly (5-90 mg, 395 patients in two trials), and compared with placebo and reference drugs. Patients subjectively evaluated pain intensity and relief using verbal categoric and visual analog scales; efficacy values included pain intensity difference (PID), summed PID, and total pain relief. Oral ketorolac 10, 12.5, 100, and 200 mg were each statistically significantly superior to placebo in all efficacy measurements, and 10 mg was equivalent to intramuscular morphine 10 mg. Intramuscular ketorolac 90 mg was superior to and 10 and 30 mg were similar to intramuscular morphine 12 mg, and all of these ketorolac doses were superior to intramuscular morphine 6 mg. Intramuscular ketorolac 10 and 30 mg were superior to intramuscular meperidine 50 and 100 mg. Ketorolac was well tolerated, with rates of adverse events generally lower than those of the opiate comparators. Ketorolac doses of 2.5 and 5 mg were less effective than higher doses; 10 mg or more resulted in faster onset of action and greater peak efficacy; 90 mg or more gave more prolonged analgesic effects.

Heparin therapy in venous thromboembolism.

Patients with pulmonary embolism or deep venous thrombosis were randomly assigned to receive either intermittent or continuous intravenous heparin therapy. In patients with an enhanced risk of bleeding, major bleeding was significantly more common during the intermittent use of heparin; in patients without these risk factors, hemorrhage occurred with equal frequency during intermittent and continuous heparin therapy. Recurrent thromboembolism was seen significantly more often in patients receiving continuous heparin therapy. Controlling the dose of heparin with coagulation tests resulted in the administration of significantly larger daily doses of heparin with intermittent injections than with continuous infusion. Therefore, the bleeding complications of intermittent heparin therapy could have been due to the higher dose, and the recurrences associated with continuous heparin therapy may have resulted from lower doses rather than from differences in the method of administration. In a small trial, arbitrary lower doses of heparin given intermittently similar to the doses of heparin given continuously resulted in fewer bleeding complications and more recurrences. In patients without risk factors for bleeding, the intermittent administration of heparin in the higher dose is preferable because of fewer recurrences and no increase in hemorrhagic complications. In patients with a high risk of bleeding, conventional doses of heparin given continuously can reduce the rate of hemorrhagic complications but will result in more recurrences.

Bilateral adrenal hemorrhage: a complication of prophylactic anticoagulation.

The following case report presents a rare complication, bilateral adrenal hemorrhage, following low dose heparin prophylaxis for deep vein thrombosis in a 59-year-old total hip replacement patient. Symptoms associated with adrenal hemorrhage included nausea, vomiting, epigastric pain, increased temperature and white blood-cell count, and a drop in the hematocrit. At no time either pre- or postoperatively were hematological studies abnormal.Adrenal hemorrhage has been documented following therapeutic doses of heparin but is exceedingly rare following low doses of the drug. It has rarely been diagnosed before death occurred. It is concluded that use of low doses of heparin for prevention of deep vein thrombosis is of limited efficacy in patients undergoing total hip replacement surgery and its routine use is therefore not recommended.

Anaerobic pleural and pulmonary infections.

Radiographic findings are reviewed for 69 patients with bacteriologically proven anaerobic infections in the thorax. On the initial films, the disease was confined to the lung parenchyma in 50%, and to the pleura in 30% of patients. The other 20% had combined pleural and parenchymal disease. Over 50% of cases had lung necrosis on the initial films, and many patients who began with a noncavitary pneumonia developed necrosis during hospitalization despite antimicrobial therapy. Once necrosis developed, resolution was slow with an average closure of 65 days for lung abscesses. Parenthymal disease was usually confined to one anatomic site. This site was almost always in a basal or posterior part of the lungs. Pleural effusions tended to progress very rapidly and always proved to be empyemas. Many empyemas occurred without recognizable pneumonic disease. A few were nosocomial, occurring as a complication of surgery, penetrating chest wounds, or subphrenic abscesses. Many patients developed empyemas as a complication of parenchymal disease, frequently while on antimicrobial therapy. Almost all empyemas required surgical drainage with either a rib resection or decortication.

Radiographic techniques for balloon-occlusion pulmonary angiography.

Pulmonary angiography was performed in 125 patients with suspected pulmonary embolism. Standard angiographic techniques were combined with balloon occlusion of pulmonary arterial branches using a double lumen catheter and contrast material injection distal to the occlusion. Vessel opacification was fluoroscopically monitored and images obtained with either a conventional cut-film camera, a spot-film camera, or cineangiography. Balloon-occlusion angiography improved image quality and contributed substantially to the radiographic diagnosis of pulmonary embolism in most patients. The technique is useful in patients too ill to undergo conventional angiography and may be performed at the bedside.

Low-dose heparin therapy in the long-term management of venous thromboembolism.

The efficacy of a six-month course of low-dose heparin therapy was compared to a conventional warfarin regimen by a prospective, controlled trial in 48 patients with pulmonary embolism or deep venous thrombosis of the legs. All subjects had complicated medical illnesses and a high risk of recurrent thromboembolism. Bleeding complications were virtually negligible during heparin therapy and occurred significantly more frequently in patients receiving warfarin. Heparin was as effective as warfarin in the prevention of recurrent thromboembolism. Patient compliance with the two treatment regimens was comparable. Self-administered, low-dose heparin therapy is a useful alternative to warfarin in the long-term management of complicated thromboembolic disorders.

Diagnostic value of tests of fibrin metabolism in patients predisposed to pulmonary embolism.

Blood tests for fibrinogen/fibrin degradation products (FDP/fdp) and soluble fibrin complexes (SFC) were performed in 100 patients at high risk for thromboembolism in order to assess the diagnostic value of these determinations in patients suspected to have pulmonary embolism. Tests were positive significantly less often in high-risk patients, and mean values were significantly lower, when compared with patients with established pulmonary embolism (P less than .001). However, no significant differences existed between high-risk patients and patients with deep venous thrombosis of the legs. Positivity rates and mean values were significantly higher in the presence of pulmonary embolism than in patients with deep venous thrombosis alone (P less than .05). Elevated FDP/fdp and SFC values are useful in the diagnosis of pulmonary embolism in high-risk patients; moreover, positive results in a patient with deep venous thrombosis suggests that pulmonary embolism has occurred.

Pulmonary manifestations of acute aspiration of gastric contents.

Radiographic manifestations of aspiration of gastric contents were reviewed in 60 patients. The findings were extremely variable, and there was no typical or characteristic appearance. Confluent and acinar infiltrates, as well as infiltrates composed of small irregular shadows, occurred singly or in a variety of combinations; the third pattern predominated in the majority of cases. Distribution was most commonly bilateral and multicentric and usually favored perihilar or basal regions, but localized or atypical densities were also observed. Patients with the most extensive radiographic abnormalities on initial studies tended to have the worst prognosis; however, mild early pulmonary infiltrates occasionally progressed to life-threatening abnormalities, and extensive initial involvement was frequently followed by a benign clinical and radiographic course. Radiographic changes often worsened for several days in uncomplicated cases, but improvement was generally manifested within the first week after aspiration. Worsening of infiltrates after initial improvement was associated with the development of bacterial pneumonia, the adult respiratory distress syndrome, and pulmonary embolism. In the appropriate clinical setting, aspiration of gastric contents should be an important diagnostic consideration in the presence of a wide variety of radiographic changes.

Noninvasive diagnosis of deep venous thrombosis by phleborheography.

Phleborheography, a recently described noninvasive test for deep venous thrombosis, was compared with leg venography in 75 patients. Acute deep venous thrombosis was accurately diagnosed by phleborheography in 24 patients, with no false-positive diagnoses. External venous compression without thrombosis was diagnosed correctly in two patients. The remaining patients appeared normal or had chronic venous disease by phleborheography; however, 11 of these had acute deep venous thrombosis by venography, for a false-negative rate of 31%. Most undetected thrombi were in small calf veins. The specificity of phleborheography is thus 100%, but the sensitivity is only 69%. Similarly, its positive predictive value is 100% and the negative predictive value is 78%. When phleborheography shows acute deep venous thrombosis, this diagnosis may be accepted with confidence and therapy chosen accordingly, without venographic confirmation. Venography may still be required to withhold anticoagulation when phleborheography is negative.

Miliary tuberculosis diagnosed by fibreoptic bronchoscopy and transbronchial biopsy.

Fibreoptic bronchoscopy with bronchial washing and trasnbronchial biopsy was performed in 8 patients with miliary tuberculosis and helped establish the diagnosis in 6 (75%). This procedure may provide a valuable adjunct to the diagnosis of miliary tuberculosis.

Radiographic features of pleural effusions in pulmonary embolism.

A prospective analysis of 155 patients with pulmonary embolism was undertaken to describe the radiographic characteristics of associated pleural effusions and related abnormalities. Approximately one half of these patients had pleural effusions. Patients with other potential causes of effusion, such as heart failure, pneumonia, or cancer, were eliminated from further analysis. In the remaining 62 patients, radiographic evidence of pulmonary infarction accompanied pleural effusions in one half of the cases. One third of patients with parenchymal consolidation had no evidence of effusion. Atelectasis and other nonspecific radiographic abnormalities occurred in less than one fifth of the cases. Typically, pleural effusions were small and unilateral, appeared soon after symptoms of thromboembolism began, and tended to reach their maximal size very early in the course of the disorder. Pulmonary infarction was associated with larger effusions that cleared more slowly and were more often bloody in appearance on thoracentesis. Chest pain occurred in all but one patient and was a valuable diagnostic clue. Pain and pleural effusions were always ipsilateral and almost always unilateral, but neither correlated well with the presence or time course of infarction. Effusions that were delayed in onset or that enlarged late in the course were associated with recurrent pulmonary embolism or superinfection. These radiographic features may be helpful in the diagnosis and management of pulmonary embolism.

Tests of fibrin metabolism in recurrent venous thromboembolism.

Fibrinogen/fibrin degradation products (FDP/fdp) and soluble fibrin complexes (SFC) were measured serially in 60 patients heparinized for pulmonary embolism or deep venous thrombosis. Eight patients had recurrent thromboembolism. In patients without recurrence, FDP/fdp and SFC tended to normalize within three to five days. In patients with recurrence, results of both tests were significantly higher on admission, and FDP/fdp values were significantly higher throughout ten days of therapy, than in patients without recurrence. The SFC values were not different between the two groups during the first six days of treatment, but again became significantly higher on the seventh day in patients with recurrence. There were no differences in clotting times, heparin dosage, or any other clinical features between patients with and without recurrence. Measurement of FDP/fdp and SFC can help identify patients at risk of recurrent thromboembolism if performed serially during treatment.

Dynamic measurement of regional ventilation and perfusion of the lung with Xe-133.

A method for measuring regional distribution of ventilation and perfusion with Xe-133 during tidal breathing was developed with normal subjects, and compared with current breath-holding techniques in patients and in animals. Normal values for a ventilation index during washin, a perfusion index, and a washout slope index were determined in both supine and upright normal subjects. Comparisons of tidal-breathing and breath-holding measurements in patients with localized bullous disease of the lung showed roughly equal values for perfusion index by the two methods, but the tidal-breathing method was more sensitive to abnormalities in ventilation index. During occlusion of branches of the pulmonary artery in animals, the tidal-breathing and breath-holding methods were again comparable in the measurement of perfusion indices, but the tidal-breathing method provided a more sensitive assessment of ventilatory changes due to partial bronchial occlusion in animals. This technique appears superior to standard methods and is well suited to dynamic measurement of regional ventilation and perfusion in a number of experimental and clinical circumstances.

Pulmonary aspiration of gastric contents.

A retrospective analysis of 50 patients who had been observed to aspirate gastric contents was performed to define better the course of patients with this syndrome. The patients invariably had a disturbance of consciousness, most commonly due to sedative drug overdose or general anesthesia. The onset of clinical signs occurred prompty after aspiration and tended to be similar in all patients, irrespective of their subsequent course or outcome. These findings usually included fever, tachypnea, diffuse rales, and serious hypoxemia. Cough, cyanosis, wheezing, and apnea were each seen in approximately one third of the cases. Apena, shock, and early severe hypoxemia were particularly ominous events. Initial roentgenograms revealed diffuse or localized alveolar infiltrates, which progressed during the next 24 to 36 hours. Subsequent clinical courses followed 3 patterns: 12 per cent of the patients died shortly after aspiration; 62 per cent had rapid clinical and radiologic improvement, with clearing, on average, within 4.5 days; 26 per cent demonstrated rapid improvement, but then had clinical and radiographic progression associated with recovery of bacterial pathogens from the sputum and a fatal outcome in more than 60 per cent. Treatment from the outset by adrenocortical steroids or antimicrobial agents had no demonstrable effect on the outcome. The clinical features of aspiration of gastric contents are characteristic and distinguish it from other forms of aspiration-related lung disease.

An improved pulmonary angiographic technique using a balloon-tipped catheter.

Selective pulmonary angiography, using injection of contrast material distal to occlusion of a lobar or segmental vessel with a balloon-tipped catheter, was performed in 33 patients suspected of having pulmonary embolism. Excellent film quality was possible with this method using specialized radiographic techniques allowing exposure of rapid-sequence spot films. Balloon-occlusion angiography contributed to, or improved on, findings on standard angiograms in 28 of 33 patients; the procedures were inconclusive or incomplete in 5 cases owing to unavoidable technical factors. In general, image quality, definition of both large and small vessels, and visualization of emboli were often superior to results obtained by routine angiography. This technique is safe, relatively easy to perform, and capable of serving as a valuable adjunct to established diagnostic procedures for pulmonary embolism.

Comparison of spontaneous and positive-pressure breathing in supine normal subjects.

Distribution of ventilation (V) and perfusion (Q) was studied with 133Xe in eight supine, normal subjects comparing spontaneous breathing (SB) and intermittent positive-pressure breathing (IPPB). Tidal volume, inspiratory flow, and breathing frequency measured during SB were closely matched during automatically triggered IPPB. V and Q in the lung bases (adjacent to the diaphragm) were decreased relative to other regions during SB and further diminished by IPPB at similar volumes. During IPPB, basilar V and Q improved when tidal volume was increased; however; spontaneous hyperinflation resulted in significantly higher basilar V and Q than large tidal volumes delivered by IPPB. Thus, changes in lung volumes and gas exchange in the supine posture are attributable to impaired V and Q in the bases but not in dependent (posterior) regions. IPPB further reduces basilar V and Q, possibly due to loss of interdependence resulting from diminished respiratory muscle contraction. These findings may explain atelectasis during prolonged IPPB in supine patients. Although large tidal volumes improve basilar V during IPPB, spontaneous deep breaths are more effective and may prevent atelectasis better than IPPB at similar tidal volumes.