Rofecoxib and tramadol do not attenuate delayed-onset muscle soreness or ischaemic pain in human volunteers

We assessed the effect of rofecoxib, a cyclo-oxygenase-2 inhibitor, and tramadol, a centrally acting analgesic, on both delayed-onset muscle soreness (DOMS) and experimentally induced ischaemic pain. We induced DOMS in 10 male and 5 female healthy volunteers by downhill running for 30 min at a 12% decline and a speed of 9 km x h(-1). We also induced ischaemic pain by finger movements with an arterial tourniquet around the arm. In a randomized, double-blind crossover format, we administered rofecoxib (50 mg, daily), tramadol (50 mg, 3 times per day), and a placebo (orally for 3 days), starting immediately after exercise. A 100 mm visual analogue scale (VAS) and McGill pain questionnaire were used to describe muscle soreness and ischaemic forearm pain 24 h after the exercise. The pressure pain threshold (PPT) in the thigh and ischaemic pain tolerance in the forearm were measured before exercise and 24 and 72 h after exercise. PPT decreased 24 h after exercise, compared with pre-exercise values (ANOVA, p < 0.05), but neither drug had any significant effect on the PPT. Neither rofecoxib nor tramadol had any effect on time of ischaemia tolerated or amount of finger activity during ischaemia. The VAS and pain-rating index, for both muscle soreness and experimental ischaemic pain, were not affected significantly by either drug. Both DOMS and ischaemic pain share peripheral and central mechanisms, yet neither are attenuated by rofecoxib or tramadol.     

Prognosis of patients with "chest pain ?cause".

All 662 patients admitted to the two coronary care units in Nottingham during 12 consecutive months were followed up prospectively for one year. At the time of discharge from hospital they were categorised according to set criteria into the following diagnostic groups: definite, probable, or possible myocardial infarction; ischaemia heart disease without infarction; chest pain ?cause; and other diagnoses. Eighty-nine patients (13% of admissions) were categorised as having chest pain ?cause. No deaths occurred among these patients during the observation period, although two were readmitted with myocardial infarction. Patients with chest pain ?cause had few problems during the year after admission, and at the end of that time 75% were in their original employment. Patients admitted with ischaemic heart disease had a similar death rate (between six weeks and one year after admission) to those with myocardial infarction, and only 36% were in their original employment one year after admission. Chest pain ?cause is a clinically useful diagnostic category to which patients may be allocated after only simple investigations.     

Prospective evaluation of eligibility for thrombolytic therapy in acute myocardial infarction.

OBJECTIVES--To determine the proportion of patients presenting with acute myocardial infarction who are eligible for thrombolytic therapy. DESIGN--Cohort follow up study. SETTING--The four coronary care units in Auckland, New Zealand. SUBJECTS--All 3014 patients presenting to the units with suspected myocardial infarction in 1993. MAIN OUTCOME MEASURES--Eligibility for reperfusion with thrombolytic therapy (presentation within 12 hours of the onset of ischaemic chest pain with ST elevation > or = 2 mm in leads V1-V3, ST elevation > or = 1 mm in any other two contiguous leads, or new left bundle branch block); proportions of (a) patients eligible for reperfusion and (b) patients with contraindications to thrombolysis; death (including causes); definite myocardial infarction. RESULTS--948 patients had definite myocardial infarction, 124 probable myocardial infarction, and nine ST elevation but no infarction; 1274 patients had unstable angina and 659 chest pain of other causes. Of patients with definite or probable myocardial infarction, 576 (53.3%) were eligible for reperfusion, 39 had definite contraindications to thrombolysis (risk of bleeding). Hence 49.7% of patients (537/1081) were eligible for thrombolysis and 43.5% (470) received this treatment. Hospital mortality among patients eligible for reperfusion was 11.7% (55/470 cases) among those who received thrombolysis and 17.0% (18/106) among those who did not. CONCLUSIONS--On current criteria about half of patients admitted to coronary care units with definite or probable myocardial infarction are eligible for thrombolytic therapy. Few eligible patients have definite contraindications to thrombolytic therapy. Mortality for all community admissions for myocardial infarction remains high.     

Intermittent claudication: is a supervised exercise class worth while?

Twenty-one patients (19 men and two women) with disabling exercise-related leg pain attended a physiotherapy department on one afternoon each week for an exercise training programme lasting one month. The clinical diagnosis of intermittent claudication and localisation of the atherosclerotic occlusions were confirmed in all but one case by pulse volume recordings and segmental Doppler systolic pressure measurements. Two patients whose symptoms worsened underwent arterial reconstruction. Post-training assessment at six months showed that the remaining 18 patients walked 80% further and performed 75% more step-ups. They also felt much healthier, having unduly restricted their activities before because they had feared the onset of ischaemic leg pain. These results suggest that supervised exercise training is a simple and effective method of treating patients with intermittent claudication.     

Long-term beta blockade: possible protection from myocardial infarction.

The clinical behaviour of 90 patients on beta-blocking drugs for established coronary heart disease who were admitted to a coronary care unit with prolonged ischaemic myocardial pain was compared with that of 90 similar patients not on this therapy. Transmural myocardial infarction was confirmed in 30 of the patients on beta-blockers and in 62 controls. A diagnosis of myocardial necrosis without infarction was made in 20 patients on beta-blockers and in 14 controls. Coronary insufficiency was diagnosed in 40 patients on beta-blockers and in 14 controls. The incidence of simus bradycardia, hypotension, syncope, and radiological pulmonary oedema was similar in the two groups. Established beta-blockade, therefore, has not been shown to prejudice the outcome of patients with coronary heart disease admitted to hospital with prolonged ischaemic myocardial pain. On the contrary, it may protect some patients from the development of a myocardial infarction.     

Patient and general practitioner delays in acute myocardial infarction

The longest component of the total delay in coming under coronary care is patient delay, and it has been suggested that public education might be used to make it shorter. The patterns of patient delay were studied in 450 patients with acute myocardial infarction uncomplicated by cardiac arrest out of hospital, of whom 243 had a previous history of ischaemic heart disease. Patient delays had a skewed distribution with a modal delay of up to one hour, a median delay of two hours, and a mean delay of 10 hours. Two thirds of patients had sought help from their general practitioners within four hours of the onset of symptoms. During the first four hours the longer that patients delayed the lower was the subsequent mortality (27%, 18%, and 9% for delays of one hour or less, up to two hours, and up to four hours, respectively), but patients who delayed four to eight hours had the highest mortality of all (38%). Neither the median value nor the pattern of patient delays was altered by a previous history of ischaemic heart disease.There were pronounced differences in doctor delays, depending on the patient''s age, delay time, and ultimate place of treatment, showing that the doctors'' behaviour was influenced before they had seen their patients. Nevertheless, the median total delay for patients aged up to 70 was one hour 35 minutes, and a higher proportion of patients were seen early after infarction than in recent hospital trials of thrombolytic treatment.These findings suggest that the patients'' call for help and the doctors'' response may be at an instinctive level according to the patients'' distress; these patterns of behaviour may be difficult to modify by public education.     

Myocardial ischaemia in patients with frequent angina pectoris.

One hundred patients with angina pectoris underwent 16-point electrocardiographic (ECG) mapping of the left hemithorax during a standardised exercise test. Forty-five patients had maximum ST-segment depression at position V5, while 35 had no ECG signs of ischaemia at this position. In 20 V5 was on the edge of the precordial area, which showed less severe ST-depression than the central positions. An Oxford ECG recorder and highspeed analyser were modified and used in 50 of the patients with daily angina for recording ST-segment changes over 24 hours. Serial 24-hour ambulatory recordings from the edge of the precordial area of ischaemia identified during exercise detected a mean of only 14 +/- SD 3% of the episodes of ST-segment changes recorded from the centre of the same area. Only 16 +/- 2% of the episodes detected by ECG were accompanied by chest pain. More episodes occurred between 4 am and 6 am than at any other time during the night. This study shows the importance of recording ECG evidence of ischaemia from the precordial position showing maximum changes during exercise. ECG evidence of ischaemia occurs more frequently than anginal pain. These objective measurements add important information to the frequency of chest pain reported by patients with ischaemic heart disease.     

Type A behaviour and ischaemic heart disease in middle aged British men.

The Bortner questionnaire, which measures aspects of type A (coronary prone) behaviour was completed by 5936 men aged 40-59 selected at random from one general practice in each of 19 British towns. The presence of ischaemic heart disease was determined at initial examination and the men were followed up for an average of 6.2 years for morbidity and mortality from myocardial infarction and for sudden cardiac death. Non-manual workers had significantly higher scores (more type A) than manual workers and the score decreased (less type A) with increasing age. After adjustment for social class and age men with higher scores had higher prevalences of ischaemic heart disease less marked for electrocardiographic evidence and more marked for response to a chest pain questionnaire (angina or possible myocardial infarction). A man''s recall of a doctor''s diagnosis of ischaemic heart disease, however, did not relate to his Bortner score. There was no significant relation between the Bortner score and the attack rate or incidence of major ischaemic heart disease events. In this study type A behaviour, as measured by the Bortner questionnaire, did not predict major ischaemic heart disease events in British middle aged men.     

Long-term Prognosis following Ventricular Fibrillation in Acute Ischaemic Heart Disease

Of 160 patients who survived ventricular fibrillation complicating acute ischaemic heart disease, 80 had had a clinically mild coronary attack. Most of the long-term survivors had ventricular fibrillation within 24 hours of the onset of symptoms. The longterm prognosis of the survivors was similar to that of patients whose myocardial infarction was not complicated by ventricular fibrillation. Those patients who survived ventricular fibrillation which occurred within four hours of the onset of symptoms were younger, usually had had a mild coronary attack, and had the most favourable longterm prognosis. The number of episodes of ventricular fibrillation did not affect adversely the long-term prognosis. Of those who at the time of review were eligible to work, 86% were fit to work and 68% were actually at work.     

Vomiting as a diagnostic aid in acute ischaemic cardiac pain.

The incidence of vomiting before the administration of analgesics was studied in 109 patients admitted to hospital as emergencies with prolonged ischaemic cardiac pain. In transmural myocardial infarction (58 patients) the incidence was 43% (anterior infarction 58%, inferior infarction 41%). Of the 23 patients with myocardial necrosis but without transmural infarction (that is, those with diffuse or subendocardial necrosis) and the 28 with coronary insufficiency but no necrosis, only one patient in each group experienced vomiting. When vomiting occurs early in association with cardiac pain transmural infarction may be expected in 90% of patients.     

Pain perception in competitive swimmers.

The pain perception of 30 competitive swimmers was studied using experimentally induced ischaemic pain. The pain thresholds and tolerances of this group were compared with those of 30 club swimmers and 26 non-competitive athletes. While pain thresholds showed little difference between the groups, pain tolerances were considerably different. Pain tolerances of the competitive swimmers varied according to the stage of the training season. The relation between ischaemic pain and that experienced during swimming training was studied using a pain questionnaire composed of several systematically structured verbal categories. Both types of pain were classified along similar dimensions, and it was concluded that the experimentally demonstrated pain tolerances could be generalized to the normal pain perception of the subjects. The origins of the enhanced pain tolerances of the competitive swimmers would seem to lie in their systematic exposure to brief periods of intense pain. These data could have relevance for the treatment of chronic pain in certain diseases.     

Arterial occlusion after cannulation.

The occurrence of ischaemic changes, arterial occlusion, and other complications which may follow percutaneous arterial cannulation was assessed in a survey of 155 patients. No patient complained of or had signs of ischaemic damage though signs of arterial occlusion were found in 33 patients (22%). These signs were significantly more common after periods of cannulation greater than six hours (43%) than after less than six hours cannulation (17%). During recovery from occlusion all patients had palpable pulsation over the artery even though blood flow seemed to be absent. By the end of follow-up blood flow had returned in 19 of the 33 occluded arteries.     

Results of the treatment of peripheral arterial diseases with PGE1

PGE1 (Prostin VR by Upjohn) was administered in the form of intra-arterial infusion to the patients with ischaemic disease of the limbs. The investigations aimed at collecting additional data contributing to the elaboration of optimal administration of the drug, its dosage and objective assessment of the obtained results. The obtained results have shown that the therapeutic efficiency of PGE1 depends on the advancement of ischaemia. Favourable clinical result was achieved in 45% of the patients manifested by the decrease of pain and healing rate. Such an effect persisted 2-7 months. An increase in serum total proteins and fibrinogen fraction and a decrease in platelet aggregation was seen during the PGE1 infusion. Skin temperature measurements and radioisotope examination with perfusion scintigraphy have shown an increase in blood flow in both muscles and other tissues in the treated patients. The obtained results confirmed a value of intra-arterial PGE1 infusion in the treatment of ischaemic limb diseases.     

United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: interim results

From 1979 to 1985, 2435 patients thought to have had a transient ischaemic attack or minor ischaemic stroke were allocated at random to receive long term blind treatment with either aspirin 600 mg twice daily (n=815), aspirin 300 mg once daily (806), or placebo (814). Treatment continued with about 85% compliance until September 1986 (mean four years). The odds of suffering one or more of four categories of event—namely, non-fatal myocardial infarction, non-fatal major stroke, vascular death, or non-vascular death—were 18% less in the two groups allocated to receive aspirin than in the group allocated to receive placebo (2p=0·01). The more relevant but less frequent composite event of disabling stroke or vascular death was reduced by only 7%; this reduction was not significantly different from zero, but nor was it significantly different from a 25% reduction. There was no definite difference between responses to the 300 mg and 1200 mg daily doses, except that the lower dose was significantly less gastrotoxic.     

Continuous narcotic infusions for relief of postoperative pain.

Relief of acute pain after surgery or trauma is still inadequate in many centres, most patients being treated with intermittent intramuscular injections of narcotic analgesics. Over the past three years continuous intravenous narcotic infusions have been used at this hospital to treat postoperative pain; recently a system has been devised whereby an hourly dose is given and the dispenser recharged every hour. The method used is cheap and reliable, and signs of overdosage may be easily checked by nursing staff. Side effects rarely occur. Fifty patients who had received intravenous infusions after undergoing major abdominal surgery were sent a questionnaire to assess postoperative pain, and the results were compared with those from 50 matched controls who had received intramuscular injections. Of those who replied, only four patients who had received the infusion had found the pain distressing compared with 13 controls. Continuous narcotic infusions are most effective in relieving postoperative pain and may be given cheaply and reliably.     

e-Transmission of ECGs for expert consultation results in improved triage and treatment of patients with acute ischaemic chest pain by ambulance paramedics

Aims

In pre-hospital settings handled by paramedics, identification of patients with myocardial infarction (MI) remains challenging when automated electrocardiogram (ECG) interpretation is inconclusive. We aimed to identify those patients and to get them on the right track to primary percutaneous coronary intervention (PCI).

Methods and results

In the Rotterdam-Rijnmond region, automated ECG devices on all ambulances were supplemented with a modem, enabling transmission of ECGs for online expert interpretation. The diagnostic protocol for acute chest pain was modified and monitored for 1 year.Patients with an ECG that met the criteria for ST-elevation myocardial infarction (STEMI) were immediately transported to a PCI hospital. ECGs that did not meet the STEMI criteria, but showed total ST deviation ≥800?µv were transmitted for online interpretation by the ECG expert. Online supervision was offered as a service if ECGs showed conduction disorders, or had an otherwise ‘suspicious’ pattern according to the ambulance paramedics.We enrolled 1,076 patients with acute ischaemic chest pain who did not meet the automated STEMI criteria. Their mean age was 63 years; 64% were men. After online consultation, 735 (68%) patients were directly transported to a PCI hospital for further treatment. PCI within 90?min was performed in 115 patients.

Conclusion

During a 1-year evaluation of the modified pre-hospital triage protocol for patients with acute ischaemic chest pain, over 100 acute MI patients with an initially inconclusive ECG received primary PCI within 90?min. Because of these results, we decided to continue the operation of the modified protocol.

     

Production of Epigastric Pain in Duodenal Ulcer by Lower Oesophageal Acid Perfusion

Thirty-six patients with duodenal ulceration were divided into group 1 (30), who had epigastric pain, and group 2 (6), who had pain in the upper abdomen but not in the epigastrium, and were studied by perfusing the lower oesophagus with dilute acid in an attempt to reproduce epigastric pain. In group 1, 25 suffered epigastric pain, indistinguishable from that which they normally had, after perfusion of 30 ml. of 0·1N HC1 in under four minutes (mean values), but none of group 2 had pain.     

Treatment of Zoster with Idoxuridine in Dimethyl Sulphoxide. Results of Two Double-blind Controlled Trials

The antiviral effect of 5% idoxuridine in dimethyl sulphoxide intermittently applied and of 40% idoxuridine in dimethyl sulphoxide continuously applied for four days to the lesions in patients with zoster of recent onset was studied in two double-blind controlled trials. Most, but not all, of the patients receiving intermittent active treatment had pain for a short period only. The effect of continuous treatment was striking: pain had disappeared within nine days in all the patients and healing was accelerated. The results were statistically significant.     

Influence of transoesophageal echocardiography on therapy and prognosis in young patients with TIA or ischaemic stroke

Objective. To determine the influence of transoesophageal echocardiography (TEE) on therapy and prognosis in patients with cryptogenic transient ischaemic attack (TIA) or ischaemic stroke under the age of 50 years. Methods and results. We evaluated all patients aged 50 and under who were referred to our university hospital for cryptogenic TIA or ischaemic stroke during the period 1 January 1996 to 31 December 2004. All patients underwent both transthoracic echocardiography (TTE) and TEE. Patients with known pre-existent heart disease, such as atrial fibrillation, were excluded. Eighty-three patients with TIA (22) and ischaemic stroke (61) were enrolled. Mean age was 39±8 years (range 18 to 50). In 30% of the patients TEE detected one or more potential cardioembolic source, compared with 10% for TTE (p=0.003). Standard treatment (aspirin 38 mg daily) was changed in 7% of the patients due to the TEE findings. Complete followup was obtained in 93% with an average of 5±3 years. Twelve recurrences occurred; two out of six patients (33%) with therapy change and ten out of 71 (14%) of the patients without therapy change had a recurrent TIA or ischaemic Stroke. Conclusion. In patients with cryptogenic TIA or ischaemic stroke, TEE is superior to TTE in the detection of a potential cardiac source of embolism. However, findings obtained by TEE only influence the already initiated treatment in a small percentage of patients. The recurrence rate both in the group with and without therapy change is high. (Neth Heart J 2009;17:373–7.)