Relief of pain by infusion of morphine after operation: does tolerance develop?

To see whether continuous intravenous infusion of opiates provides more effective postoperative relief of pain than conventional intramuscular injection these regimens were compared in a prospective double blind trial. Thirty patients undergoing elective cholecystectomy were allocated randomly to receive an infusion of morphine or an infusion of placebo (control group) for 24 hours. Both groups were allowed supplementary morphine boluses as requested. During the first 48 hours after operation the degree of pain was almost identical between the groups. Surprisingly, the group that was given the infusion of morphine received as much supplementary morphine as the control group during the first 24 hours and appreciably more during the 24 hours after the infusion had been withdrawn. Nausea and vomiting were more prevalent among the patients given the infusion of morphine. These results suggest that continuous infusion of morphine may be an inferior regimen to intermittent bolus administration in the relief of postoperative pain. This may be explained by the development of tolerance in patients who received the infusion of morphine.     

Postoperative analgesia with controlled-release morphine sulphate: comparison with intramuscular morphine.

Fifty patients undergoing hysterectomy or cholecystectomy took part in a trail of postoperative analgesia provided by either intramuscular morphine or controlled-release morphine sulphate tablets orally. Respiratory function and plasma catecholamine concentrations were measured after operation and pain was assessed by using a linear analogue scoring method. Controlled-release morphine sulphate produced comparable pain relief with that of intramuscular morphine, and depression of respiratory function after operation was similar with the two analgesic regimens. The mean total dose of drug per patient given over 48 h to patients undergoing hysterectomy was 115 mg for morphine sulphate and 53 mg for morphine. Patients undergoing cholecystectomy received 130 mg morphine sulphate or 76 mg morphine. There was more sedation after operation in those patients undergoing hysterectomy who received morphine sulphate tablets. Morphine sulphate tablets produced satisfactory postoperative analgesia compared with intramuscular morphine: both regimens were acceptable to the patients.     

Intravenous morphine infusion (IMF) to drug-naive, conscious rats evokes bradycardic, hypotensive effects, but pressor actions are elicited after IMF to rats previously given morphine

Hemodynamic (blood pressure and heart rate) responses of conscious drug-naive rats were studied following intravenous (i.v.) infusion of sterile saline, morphine sulphate, and then naloxone hydrochloride, as well as of other groups previously injected with morphine sulphate. Those groups chronically given morphine sulphate received twice daily injections of morphine sulphate (5 mg/kg, s.c. per injection) for 3 or 6 days before testing with the i.v. infusion of morphine sulphate. Drugs were infused (135 microL/min) through an indwelling femoral venous catheter via a Harvard infusion pump, and blood pressure was recorded from the abdominal aorta via a femoral arterial catheter. Other pretreatment studies were done to determine the receptor mechanisms mediating the blood pressure responses of drug-naive and chronic morphine-treated rats, whereby equimolar doses (0.32 mumol) of specific receptor antagonists were given as a bolus i.v. injection 5 min after saline but before subsequent infusion with morphine sulphate. Intravenous infusion of morphine sulphate (7.5 mg/kg total over 15 min) to drug-native rats caused a transient but precipitous fall in mean arterial pressure and mean heart rate with an associated rise in mean pulse pressure; these effects were blocked in other groups pretreated with atropine. Interestingly, however, rats chronically injected with morphine sulphate for 3 days previously evoked a transient pressor response when subsequently infused i.v. with morphine sulphate, actions that were blocked in other groups when pretreated i.v. with 0.32 mumol of phentolamine, yohimbine, prazosin, or guanethidine. A greater and persistent pressor response occurred following morphine infusion to groups of rats previously injected over 6 days with morphine sulphate, which was associated with tachycardia during the later stages of the 15-min morphine sulphate infusion period. The prolonged pressor and tachycardic responses of this 6-day chronically injected group were completely blocked in another group pretreated i.v. with both phentolamine and propranolol (0.32 mumol). The results suggest that morphine sulphate infusion to conscious, drug-naive rats evokes classical hypotensive effects due to decreases in mean heart rate caused by activation of parasympathetic vagal activity. With 3 or 6 days of chronic morphine sulphate administration beforehand, subsequent i.v. infusion of morphine sulphate evoked pressor actions felt to be caused by a progressive activation of the sympathetic nervous system.(ABSTRACT TRUNCATED AT 400 WORDS)     

Optimising antiemesis in cancer chemotherapy: efficacy of continuous versus intermittent infusion of high dose metoclopramide in emesis induced by cisplatin.

Thirty three untreated patients being given cisplatin received metoclopramide (7 mg/kg) for antiemesis by either continuous or intermittent infusion in a random order. Each patient received intravenous dexamethasone in addition. High pressure liquid chromatography was used to measure plasma concentrations of metoclopramide. The two regimens were evaluated for antiemetic efficacy and the incidence of side effects. The intermittent metoclopramide regimen resulted in peak and trough plasma concentrations of metoclopramide with accumulation at eight hours, while the loading dose and continuous infusion resulted in mean plasma concentrations greater than 0.85 micrograms/ml (2.8 mumol/l) throughout the eight hour period. The continuous infusion was associated with a significant improvement in nausea and vomiting and reduction in diarrhoea. Major control of emesis (two episodes or fewer) was achieved in 27 patients receiving continuous metoclopramide compared with 18 receiving intermittent metoclopramide.     

Respiratory effects of analgesia after cholecystectomy: comparison of continuous and intermittent papaveretum.

Two methods of administering papaveretum for relieving postoperative pain were compared in two groups of patients who had undergone cholecystectomy. In one group a loading dose of papaveretum was administered by continuous intravenous infusion (1 mg/min) until the patient could breathe deeply without undue pain. Eight times this loading dose was given as a continuous intravenous infusion over the subsequent 48 hours. This regimen was compared with a conventional intermittent intramuscular dose (0.25 mg/kg at four hourly intervals as necessary) in a second group of patients. The intravenous regimen relieved pain better than the intramuscular regimen, which may have reflected the larger dose of papaveretum given to the intravenous group, but it was accompanied by a greater degree of respiratory depression and potentially life-threatening changes in respiratory pattern. These findings suggest that the fear which often accounts for inadequate postoperative pain relief-that larger dose of analgesics will cause respiratory complications-is well founded.     

Peripheral regional analgesia with femoral catheter versus intravenous patient controlled analgesia after total knee arthroplasty: a prospective randomized study

The aim of this study is to compare the effects of femoral analgesia (FA) with 0.25% levobupivacain and intravenous patient controlled analgesia (PCA) with morphine on postoperative pain assessed by a visual-analog scale (VAS) score and their complications during the first 24 postoperative hours after the a total knee arthroplasty in a prospective randomized study. Secondary outcomes included: morphine use, patient satisfaction, complication of analgesia and duration of hospital stay. We analyzed 71 patients with an ASA score of II or III. The patients were randomized into two groups: group PCA (n = 36) was given the PCA pump, which contained morphine; and group FA (n = 35) was given first a bolus dose, then a continuous infusion 0.25% levobupivacain via a femoral catheter. The assessment of VAS was performed every 2 hours. There were no differences between the PCA and FA groups regarding demographic characteristics, operation duration, ASA score distribution, duration of hospital stay and satisfaction with analgesia (although there were more satisfied patients in the FA group). Significant differences were noted in the quantity of morphine used (higher values were in the PCA group; p < 0.001). More complications were recorded in PCA group (p < 0.001). The VAS score was lower in the FA group (p < 0.001). The highest difference occurred 4 hours after the operation, with the PCA group having significantly higher VAS score values compared to the FA group. Femoral analgesia leads to a stronger pain relief with less side effects, less morphine use and more patient satisfaction than intravenous PCA with morphine.     

A method for maintaining normoglycemia during labour and delivery in insulin-dependent diabetic women.

The effectiveness of combining the subcutaneous administration of short- and intermediate-acting insulin with the intravenous infusion of glucose in maintaining normoglycemia during labour and delivery in insulin-dependent diabetic women was tested. Fifty women were given intermediate-acting insulin twice daily in doses that were fractions of their usual dose, based on the projected duration of labour. In addition, they were given regular (i.e., short-acting) insulin every 6 hours, the dose being 1% of their total daily insulin dose for every increase of 10 mg/dl above 100 mg/dl (5.6 mmol/l) in the plasma glucose level 1 hour previously; the levels were measured every 3 hours. All the patients were fasting and received a basal intravenous infusion of 6 g/h of glucose; the rate of infusion was increased by 1 g/h for every decrease of 10 mg/dl in the plasma glucose level below 100 mg/dl. The mean plasma glucose levels (+/- standard deviation) were 90 +/- 46 mg/dl after 3 hours of labour, 92 +/- 35 mg/dl after 6 hours, 97 +/- 49 mg/dl after 9 hours and 107 +/- 65 mg/dl after 12 hours. With only one exception, in a premature infant, the 5-minute Apgar scores were identical to those of the infants of nondiabetic women.     

Chromium Infusion In Hospitalized Patients with Severe Insulin Resistance: A Retrospective Analysis

ObjectiveTo investigate the effects of intravenous chromium on serum glucose and insulin infusion rates in hospitalized patients with severe insulin resistance.MethodsIn this retrospective study, we reviewed hospital records from January 1, 2008, to December 1, 2008, to identify patients for whom intravenous chromium was ordered at our academic medical center. To be included, patients were required to demonstrate profound insulin resistance and uncontrolled hyperglycemia (defined as the inability to achieve a blood glucose value less than 200 mg/ dL during the 12 hours before chromium was given despite administration of continuous insulin infusion at a rate of 20 or more units/h) and to have received a continuous infusion of chromium chloride at 20 mcg/h for 10 to 15 hours for a total dose of 200 to 240 mcg.ResultsFourteen patients met our inclusion criteria. Over the hour preceding intravenous chromium infusion, the mean ± standard deviation rate of insulin infusion was 31 ± 15 units/h, and blood glucose was 326 ± 86 mg/dL. Twelve hours after the initiation of chromium, these values were 16 ± 16 units/h and 162 ± 76 mg/dL, respectively (P = .011 for difference in mean insulin rate from baseline, P <.001 for difference in mean blood glucose from baseline) and 24 hours after, these values were 12 ± 15 units/h and 144 ± 48 mg/dL, respectively (P <.001 for both).ConclusionsIntravenous chromium decreases insulin needs and improves glucose control at 12 and 24 hours compared with baseline values. Chromium appears to improve hyperglycemia and insulin resistance in acutely ill patients and represents a potential new therapy. Future prospective randomized controlled trials are needed to confirm these results. (Endocr Pract. 2012;18:394-398)     

Incidence of hematoma associated with ketorolac after TRAM flap breast reconstruction

Ketorolac is frequently used as an adjunct for postoperative pain relief, especially by anesthesiologists during the immediate postoperative period. It can be used alone as an analgesic but is more often used to potentiate the actions of narcotics such as morphine or meperidine in an attempt to reduce the total dose and side effects of those drugs. The manufacturer of ketorolac cautions against its use in patients who have a high risk of postoperative bleeding, for fear of increasing the risk of hematoma, but the risk in transverse rectus abdominis musculocutaneous (TRAM) flap patients has never been reported. In a study of 215 patients who had undergone TRAM flap breast reconstruction, it was determined that patients who received intravenous ketorolac (n = 65) as an adjunct to their treatment with morphine administered by use of a patient-controlled analgesia device required less morphine (mean cumulative dose, 1.39 mg/kg) than did patients who did not receive ketorolac (n = 150; mean cumulative dose, 1.75 mg/kg; p = 0.02). There was no increase in the incidence of hematoma in patients who were treated with ketorolac. The data presented in this study suggest that the use of intravenous ketorolac does reduce the need for narcotics administration in patients undergoing TRAM flap breast reconstruction, without significantly increasing the risk of hematoma.     

Continuous intravenous infusion versus intermittent administration of streptokinase in patients with deep venous thrombosis of the lower extremity]

In a multicenter randomized trial, the efficacy and safety of two streptokinase (SK) dosage regimens have been evaluated in patients with proximal deep vein thrombosis of inferior limbs. Twenty-nine patients received SK by a continuous intravenous infusion (250,000 IU as initial dose, 100,000 IU/h as maintenance dose), and 26 patients were treated with intermittent SK administration (500,000 IU as initial dose, followed by 250,000 IU every 12 h). Thrombolytic therapy was continued for 4 days, then the patients received heparin for 5 days and oral anticoagulant for 3 months. The results of treatment as judged by phlebographic examinations were similar in the two groups. Complete, substantial or partial thrombolysis was achieved in 52% of patients in the continuous infusion group and in 58% of patients in the intermittent treatment group. During SK administration, major bleeding complications occurred in 6 patients treated by continuous infusion and in 2 of the second group. The results showed that the intermittent SK administration is as effective and safe as the method of continuous SK infusion in the treatment of deep vein thrombosis.     

The effects of prolonged ketamine-xylazine intravenous infusion on arterial blood pH, blood gases, mean arterial blood pressure, heart and respiratory rates, rectal temperature and reflexes in the rabbit

The prolonged and safe maintenance of general anesthesia in rabbits with commonly used injectable agents is difficult. Protracted, stable anesthesia with short recovery time has been described in humans using continuous intravenous infusion of ketamine with or without sedatives, muscle relaxants and paralytics. This study evaluated the anesthetic plane achieved and respiratory and cardiovascular effects produced with a ketamine-xylazine intravenous infusion in New Zealand White rabbits. Ten female rabbits were anesthetized with intramuscularly administered ketamine hydrochloride (35 mg/kg) and xylazine hydrochloride (5 mg/kg) after the preanesthetic, baseline measurements of arterial blood pO2, pCO2 and pH and heart and respiratory rates were recorded. The above parameters as well as mean arterial blood pressure, righting, palpebral, pedal, and jaw reflexes were monitored ten minutes after the intramuscularly administered dosage and throughout 4 hours of infusion. Results showed moderate hypotension (21.2% deviation from normal, p less than 0.008) and profound hypoxemia (45% deviation from baseline, p less than 0.001) 10 minutes after the intramuscularly administered induction dosage. Then, the 4 hour infusion of ketamine (1 mg/minute) and xylazine (0.1 mg/minute) was started. Hypotension progressed (49.1% deviation from normal, p less than 0.008), but hypoxemia and hypercarbemia gradually improved with no resultant change (p greater than 0.1) in arterial pH. There was no significant change (p greater than 0.1) in respiratory rate but varying qualities of respiration were observed. Both mean arterial pO2 and pCO2 values returned to baseline within 20 minutes after completion of infusion. Heart rate and rectal temperature remained stable during the trial. The righting reflex was abolished in all rabbits throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postoperative morphine requirements of free TRAM and DIEP flaps

In a review of the charts of 158 patients who had undergone breast reconstruction with free transverse rectus abdominis musculocutaneous (TRAM) or deep inferior epigastric perforator (DIEP) flaps and who were treated for postoperative pain with morphine administered by a patient-controlled analgesia pump, the total dose of morphine administered during hospitalization for the flap transfer was measured. Patients whose treatment was supplemented by other intravenous narcotics were excluded from the study. The mean amount of morphine per kilogram required by patients who had reconstruction with DIEP flaps (0.74 mg/kg, n = 26) was found to be significantly less than the amount required by patients who had reconstruction with TRAM flaps (1.65 mg/kg; n = 132; p < 0.001). DIEP flap patients also remained in the hospital less time (mean, 4.73 days) than did free TRAM flap patients (mean, 5.21 days; p = 0.026), but the difference was less than one full hospital day. It was concluded that the use of the DIEP flap does reduce the patient requirement for postoperative pain medication and therefore presumably reduces postoperative pain. It may also slightly shorten hospital stay.     

Efficacy of the pain pump catheter in immediate autologous breast reconstruction

The purpose of the investigation was to evaluate the efficacy of a slow bupivacaine infusion at postoperative surgical sites in immediate breast reconstruction patients. This prospective study included 16 patients who underwent autologous breast reconstruction with a latissimus dorsi pedicled flap immediately after mastectomy. A two-site infusion kit with dual split-flow catheters was secured at the operative sites before skin closure. A spring-loaded disposable pump then infused 0.25% bupivacaine at a rate of 2.08 cc per catheter per hour for 48 continuous hours. Patient pain levels, nausea/emesis, and oral and intravenous narcotic use were then recorded at 12-hour intervals. Medication use was converted to pain units for results comparison (one pain unit was defined as the equivalent of 10 mg of intravenous morphine). A retrospective control group comprised 16 consecutive patients from December of 1999 to October of 2002 who underwent the same surgery by the same surgeon using oral and intravenous pain medications. The experimental group demonstrated a more than fivefold decrease in the use of oral and intravenous pain medications compared with the historical controls (6.7 versus 1.7 pain units) (p < 0.001). The overall pain experienced by the catheter patients was nearly twofold less than the pain experienced by those without the catheter (1.8 versus 3.4 on the visual analog pain scale) (p < 0.017). Twenty-eight percent of the experimental group experienced nausea/emesis compared with 61 percent in the control group. No complications occurred with the use of the pain pump catheter. A 48-hour infusion of 0.25% bupivacaine significantly decreases the need for postoperative narcotics and the over-all pain experience in immediate breast reconstruction patients. This effective form of pain control may alleviate patient concerns of postoperative pain and may safely downstage many plastic surgery procedures, such as immediate breast reconstruction, and many cosmetic procedures to same-day status when the primary indication for admission is pain management.     

Isoflurane compared with midazolam for sedation in the intensive care unit.

OBJECTIVE--To compare isoflurane with midazolam for sedation of ventilated patients. DESIGN--Randomised control study. Setting--Intensive care unit in university teaching hospital. PATIENTS--Sixty patients aged 18-76 who required mechanical ventilation. INTERVENTIONS--Sedation with either 0.1-0.6% isoflurane in an air-oxygen mixture (30 patients) or a continuous intravenous infusion of midazolam 0.01-0.20 mg/kg/h (30 patients). Sedation was assessed initially and hourly thereafter on a six point scale. Incremental intravenous doses of morphine 0.05 mg/kg were given for analgesia as required. The trial sedative was stopped when the patient was judged ready for weaning from ventilatory support or at 24 hours (whichever was earlier). END POINT--Achievement of a predetermined level of sedation for as much of the time as possible. MAIN RESULTS--Isoflurane produced satisfactory sedation for a greater proportion of time (86%) than midazolam (64%), and patients sedated with isoflurane recovered more rapidly from sedation. CONCLUSION--Isoflurane is a promising alternative technique for sedation of ventilated patients in the intensive care unit.     

静注硫酸镁对腰硬联合麻醉患者术后疼痛和寒战反应的影响

目的:探讨腰硬联合麻醉中静脉输注50 mg/kg和25 mg/kg两种剂量的硫酸镁对术后镇痛和寒战的的影响。方法:90名腰硬联合麻醉(CSEA)下行全子宫切除术的患者随机分成3组。在腰麻注药后即刻,MGI组30分钟内静脉输注硫酸镁25 mg/kg继以10 mg/kg/h的速度输注至手术结束;MGⅡ组输注硫酸镁50 mg/kg,然后以10 mg/kg/h的速度输注;C组注入等量生理盐水。观察术后24小时的疼痛评分(视觉模拟评分法:VAS),术后镇痛药物的用量,寒战的发生率。结果:三组术后镇痛用药量由低到高依次为MGII组,MGI组,C组(P<0.001)。术后VAS评分,MGII组较C组减少,(P<0.05);在12 h,24 h,MGII组较MGI组减少,MGI组在2 h,4 h较C组减少(P<0.05)。术后寒战在C组发生率最高,在MGI组与MGII组发生率少,组间有统计学差异(P=0.007)。结论:腰硬联合麻醉中静脉输注两种剂量的硫酸镁均可以改善术后镇痛,减少术后寒战的发生率,大剂量硫酸镁更有效,但也可能伴随更大的血流动力学波动。     

A xylazine infusion regimen to provide analgesia in sheep.

The efficacy of continuous low-dose xylazine infusion following an initial loading dose in providing analgesia in sheep was examined using an algesimetry method based on a leg lifting response to an electrical stimulus. Sheep received a 5 mg intramuscular injection of xylazine followed by continuous infusion of intravenous xylazine (2mg/h) for 90 min. This treatment resulted in significant increases in the level of current required to elicit a leg lifting response (287% of baseline) and steady state analgesia was maintained from 10 min after the start of the infusion until the end of the experimental period. This protocol appears to be a simple and effective regimen for providing steady state analgesia in sheep.     

Subcutaneous narcotic infusions for cancer pain: treatment outcome and guidelines for use.

OBJECTIVE: To provide guidelines for the institution and maintenance of a continuous subcutaneous narcotic infusion program for cancer patients with chronic pain through an analysis of the narcotic requirements and treatment outcomes of patients who underwent such therapy and a comparison of the costs of two commonly used infusion systems. DESIGN: Retrospective study. SETTING: Tertiary care facilities and patients'' homes. PATIENTS: Of 481 patients seen in consultation for cancer pain between July 1987 and April 1990, 60 (12%) met the eligibility criteria (i.e., standard medical management had failed, and they had adequate supervision at home). INTERVENTION: Continuous subcutaneous infusion with hydromorphone hydrochloride or morphine started on an inpatient basis and continued at home whenever possible. OUTCOME MEASURES: Patient selectivity, narcotic dosing requirements, discharge rate, patient preference for analgesic regimen, side effects, complications and cost-effectiveness. RESULTS: The mean initial maintenance infusion dose after dose titration was almost three times higher than the dose required before infusion (hydromorphone or equivalent 6.2 v. 2.1 mg/h). Eighteen patients died, and the remaining 42 were discharged home for a mean of 94.4 (standard deviation 128.3) days (extremes 12 and 741 days). The mean maximum infusion rate was 24.1 mg/h (extremes 0.5 and 180 mg/h). All but one of the patients preferred the infusion system to their previous oral analgesic regimen. Despite major dose escalations nausea and vomiting were well controlled in all cases. Twelve patients (20%) experienced serious systemic toxic effects or complications; six became encephalopathic, which necessitated dose reduction, five had a subcutaneous infection necessitating antibiotic treatment, and one had respiratory depression. The programmable computerized infusion pump was found to be more cost-effective than the disposable infusion device after a break-even point of 8 months. CONCLUSIONS: Continuous subcutaneous infusion of opioid drugs with the use of a portable programmable pump is safe and effective in selected patients who have failed to respond to standard medical treatment of their cancer pain. Dose titration may require rapid dose escalation, but this is usually well tolerated. For most communities embarking on such a program a programmable infusion system will be more cost-effective than a disposable system.     

Brittle diabetes: long-term control with a portable,continuous, intravenous insulin infusion system.

A young woman had severe brittle diabetes mellitus that was critically unmanageable with all conventional insulin treatment. Continuous subcutaneous and intramuscular infusions of insulin also failed to control her metabolic instability. Use of a continuous intravenous infusion, however, whereby a portable, variable-rate, battery-operated syringe pump delivered insulin through a subcutaneously tunnelled central venous catheter, resulted in good control. When she was receiving hourly intramuscular insulin injections (a mean of 778 IU daily) mean blood glucose concentrations had been 22.1 +/- 1.4 mmol/l (398 +/- 25 mg/100 microliters). After she had received the intravenous infusion for one month as an outpatient mean blood glucose concentration was 8.2 +/- 0.46 mmol/l (148 +/- 8 mg/100 microliters) and only 80 IU insulin daily was required. Follow-up after over five months of use showed that few complications had occurred. The system is simple to use and safe, and the diabetes had been stabilised such that she could enjoy a near-normal life style.     

Transfer of sulphur to the digestive tract of sheep.

The transfer of sulphate from plasma to digestive tract and from digestive tract to plasma in crossbred sheep was estimated by the use of isotope dilution techniques with Na235SO4. The passage of 35S along the digestive tract was simultaneously measured by reference to two inert radioactive markers infused intraruminally. In the first experiment, three sheep given a roughage-based diet containing 174 +/- 7 mg S/day received an intravenous infusion of Na235SO4 for 7 days before collections were made of plasma and of digesta from the rumen, abomasum and terminal ileum. Similar collections were made in the second experiment in which four sheep received intraruminal infusions of Na235SO4. From estimates of infusion rate of 35S, specific radioactivity of 35S in plasma and digesta and rate of flow of sulphur in the digestive tract the following calculations were made: The transfer of sulphate from the plasma to the rumen was calculated as 29 mg S/day. Of this only 12 mg S/day passed as organic sulphur in digesta from the stomach. As the net gain of sulphur in the stomach in this experiment was 153 mg/day, sulphate transferred from the plasma contributed only a small amount of sulphur derived from endogenous sources in the stomach. In contrast, the substantial passage of 35S into the intestinal lumen during intravenous infusion of 35SO4 suggested that 38 and 41 mg S/day of the 236 and 145 mg organic S/day flowing from the small and large intestine respectively was derived from plasma sulphate, corresponding to about 26% of the dose.     

Intravenous beta agonist in severe acute asthma.

STUDY OBJECTIVE--To determine whether salbutamol is more effective in treating severe asthma when given intravenously or by inhalation. DESIGN--Randomised trial of short term response to intravenous versus nebulised salbutamol in acute severe asthma. SETTING--District general hospital (secondary care centre). PARTICIPANTS--76 patients aged 16-70 admitted to hospital with acute severe asthma (peak expiratory flow rate less than 50% of predicted) during study period. Five withdrawn because of adverse effects of treatment or non-response. Of remaining 71, 34 allocated to nebuliser group and 37 to intravenous treatment group. Patients with history of cardiovascular disease or recent corticosteroid or intravenous bronchodilator treatment excluded. Admission characteristics similar in the two groups. INTERVENTIONS--All patients given 5 mg nebulised salbutamol on admission before randomisation plus 200 mg hydrocortisone bolus intravenously and 35% inspired oxygen throughout. Nebuliser group received two more 5 mg doses of nebuliser salbutamol at 30 minutes and 2 hours; intravenous group received 4 hours'' continuous salbutamol infusion (12 micrograms/min) starting at 30 minutes plus supplementary intravenous potassium chloride. No other bronchodilators used. ENDPOINT--Change in peak expiratory flow rate over 4 hours. MEASUREMENTS and MAIN RESULTS--Peak expiratory flow rate improved more in intravenous group (25.2%) than in nebuliser group (14.3%) (p less than 0.01, 95% confidence interval 2.4 to 19.1%). Tachycardia caused two withdrawals from intravenous group; non-response caused three withdrawals from nebuliser group. CONCLUSIONS--Intravenous salbutamol is more effective than nebulised salbutamol in acute severe asthma but may have unacceptable cardiovascular effects.