Patient-controlled analgesic infusions: alfentanil versus morphine.

Previously, we found that cancer patients using a pharmacokinetically based patient-controlled intravenous infusion system (PKPCA) to regulate their own morphine infusion rates achieved more relief from oral mucositis pain than similar patients using morphine by bolus-dose PCA. In this study, we employed the PKPCA system to compare efficacy and side-effect intensities of 2 mu-selective opioid analgesics, alfentanil and morphine, in bone marrow transplant (BMT) patients self-administering the drugs to relieve pain from oral mucositis. Patients using morphine by PKPCA obtained more pain relief than patients regulating their own alfentanil infusions during the first 4 days of continuous opioid infusion therapy. Side-effect intensities did not differ between the 2 study groups. In contrast to patients using morphine for 4-14 days, those receiving alfentanil by PKPCA required unexpectedly high plasma concentrations of the drug to obtain equivalent pain relief. Our results indicate that either the relative potencies of these 2 mu-selective opioids differ from previous estimates or analgesic tolerance developed to alfentanil but not to morphine. We conclude that alfentanil has similar efficacy in control of prolonged pain in BMT patients, but the utility of alfentanil in long-term pain management may be limited by relatively rapid tolerance onset.     

Comparison of intermittent bolus with continuous infusion of epidural morphine in the treatment of severe cancer pain.

Twenty-eight patients with severe pain due to cancer, who could no longer obtain acceptable pain relief from optimised doses of oral opioids, were entered into a study which compared pain relief, satisfaction with pain therapy and estimates of neuropsychological functioning during treatment with spinally administered (i.e., epidural and intrathecal) morphine as either repeated bolus doses or as a continuous infusion. These measures of efficacy and side effects were repeated every 2 weeks until either the patient died (82% of patients), withdrew from the study or were no longer able to complete the tests due to deterioration of their condition. The mean (range) duration of treatment was 169 (6-537) days for those patients receiving continuous infusion and 140 (28-378) days for those patients receiving repeated bolus doses. There was no significant difference in visual analogue pain scores, pain relief scores and satisfaction scores between the bolus and infusion groups. Furthermore, low pain scores and high pain relief scores indicated that both treatment modalities provided effective pain control. Similarly, there was no significant difference between the two groups in the various tests used to assess depression or neuropsychological function (i.e., memory, vigilance, attention and processing). There was a significantly greater degree of dose escalation in patients receiving continuous infusion compared to patients receiving repeated bolus doses. For 6 patients in the infusion group the catheter was sited in the intrathecal space, as the dose requirements by the epidural route exceeded the delivery capacity of the pump. For 4 patients in the bolus group the catheter was similarly sited, due to pain on injection and leakage/blockage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of continuous versus intermittent furosemide administration in postoperative pediatric cardiac patients.

OBJECTIVE: To compare the effects of furosemide administered by intermittent iv infusion vs. continuous iv infusion on urine output, hemodynamic variables, and serum electrolyte concentrations. DESIGN: Prospective, randomized trial. SETTING: Pediatric ICU. PATIENTS: Postoperative pediatric cardiac patients. INTERVENTIONS: Patients were assigned to either the continuous iv infusion or the intermittent infusion groups. The intermittent group received 1 mg/kg iv of furosemide every 4 hrs to be increased by 0.25 mg/kg iv every 4 hrs to a maximum of 1.5 mg/kg iv if the urine output was less than 1 mL/kg.hr. The continuous infusion group received an initial furosemide dose of 0.1 mg/kg iv (minimum 1 mg) followed by an iv infusion rate of 0.1 mg/kg.hr of furosemide to be doubled every 2 hrs to a maximum of 0.4 mg/kg.hr if the urine output was less than 1 mL/kg.hr. MEASUREMENTS AND MAIN RESULTS: Demographic variables, fluids, electrolyte and inotropic requirements were the same in both groups. A significantly (p = .045) lower daily dose of furosemide (4.90 +/- 1.78 vs. 6.23 +/- 0.62 mg/kg.day) in the continuous iv infusion group produced the same 24-hr urine volume as that of the intermittent group. There was more variability in urine output in the intermittent group as well as more urinary losses of sodium (0.29 +/- 0.15 vs. 0.20 +/- 0.06 mmol/kg.day, p = .0007) and chloride (0.40 +/- 0.20 vs. 0.30 +/- 0.12 mmol/kg.day, p = .045). CONCLUSION: Furosemide administered by continuous iv infusion is advantageous in the post-operative pediatric patient because of a more controlled and predictable urine output with less drug requirement and less urinary loss in sodium and chloride.     

Efficacy of continuous versus intermittent morphine administration after major surgery in 0-3-year-old infants; a double-blind randomized controlled trial

A randomized double-blind clinical trial compared the efficacy of 10 microg/kg/h morphine continuous intravenous infusion (CM) with that of 30 microg/kg morphine (IM) every 3h after major abdominal or thoracic surgery, in 181 infants aged 0-3 years. Efficacy was assessed by the caregiving nurses with the COMFORT 'behavior' and a visual analogue scale (VAS) for pain, every 3h in the first 24h after surgery. Random regression modeling was used to simultaneously estimate the effect of randomized group assignment, actual morphine dose (protocol dosage plus extra morphine when required), age category, surgical stress, and the time-varying covariate mechanical ventilation on COMFORT 'behavior' and the observational VAS rated pain, respectively. Overall, no statistical differences were found between CM and IM morphine administration in reducing postoperative pain. A significant interaction effect of condition with age category showed that the CM assignment was favorable for the oldest age category (1-3 years old). The greatest differences in pain response and actual morphine dose were between neonates and infants aged 1-6 months, with lower pain response in neonates who were on average satisfied with the protocol dosage of 10 microg/kg/h. Surgical stress and mechanical ventilation were not related to postoperative pain or morphine doses, leaving the inter-individual differences in pain response and morphine requirement largely unexplained.     

Paralysis in the critically ill: intermittent bolus pancuronium compared with continuous infusion

OBJECTIVES: To compare recovery times from neuromuscular blockade between two groups of critically ill patients in whom pancuronium was administered by continuous infusion or intermittent bolus injection. To compare the mean pancuronium requirements (milligrams per kilogram per hour) and to assess the incidence of prolonged recovery times (>12 hrs) and residual muscle weakness. DESIGN: Prospective, observational cohort. SETTING: Intensive care unit in a university-affiliated hospital. PATIENTS: A total of 30 mechanically ventilated patients who required pharmacologic paralysis. Patients were excluded if they had renal failure (creatinine clearance <30 mL/min), heart rate >130 beats/min, hepatic failure, peripheral nerve disease or myopathy, stroke, spinal cord damage, or myasthenia gravis. INTERVENTIONS: Patients were assigned to receive pancuronium either by continuous infusion (n = 14) or intermittent bolus (n = 16). Depth of paralysis was titrated to maintain one or two responses to Train-of-Four stimulation with an accelerograph and desired clinical goals. Recovery time was defined as time from discontinuation of muscle relaxant until the amplitude of the fourth twitch, measured every 15-30 min using an accelerograph, was 70% the amplitude of the first twitch (Train-of-Four > or = 0.7). MEASUREMENTS AND MAIN RESULTS: These patients included the only three patients with status asthmaticus in our study. The groups were similar with respect to age, sex, weight, Acute Physiology and Chronic Health Evaluation II score, mode of ventilation, creatinine clearance, indications for paralysis, and duration of pancuronium administration. The median time for patients to recover from paralysis was 3.5 hrs (95% confidence interval, 1.82-5.18) in the infusion group vs. 6.3 hrs (95% confidence interval, 3.40-9.19) in the intermittent bolus group (p = .10). Less drug was administered in the intermittent group (mean, 0.02+/-0.01 mg/kg/hr) than by infusion (mean, 0.04+/-0.01 mg/kg/hr; p < .001). Six patients (five in the infusion group and one in the intermittent group) developed persistent severe muscle weakness. In addition, six different patients (three from each group) had prolonged recovery >12 hrs. CONCLUSIONS: Our study suggests that recovery time after paralysis with continuous infusion is faster than that after intermittent bolus injection. Although more pancuronium was administered in the continuous-infusion group, recovery time was not prolonged as a consequence. It is uncertain whether pancuronium given by infusion increases the risk of persistent muscle weakness.     

Comparative study on the pharmacodynamics of cisatracurium: continuous infusion or intermittent bolus injection

ObjectiveTo explore a better administration way through comparison of the pharmacodynamics of cisatracurium administered by continuous infusion or intermittent bolus injection.MethodsThirty patients (ASAI-II) who had no neuromuscular disease and underwent selective surgery under general anesthesia were randomly divided into group I and II (each group with 15 patients). In group I, patients received cisatracurium by continuous infusion and in group II, by intermittent bolus injection. The responses of adductor pollicis to train-of-four (TOF) stimulation were monitored. The duration of neuromuscular blockade, recovery index and total dose of cisatracurium consumption were recorded in the two groups. Intravenous anesthesia was used for anesthesia induction and sevoflurane inhalation for maintenance of anesthesia.ResultsThe mean infusion rate was significantly lower in group I (0.78 ± 0.15 μg.kg^? 1.min^? 1) than in group II (1.09 ± 0.33 μg.kg^? 1.min^? 1) (P < 0.05). There was no significant difference in duration of neuromuscular blockade between the two groups (P > 0.05). The recovery index was 13.13 ± 3.36 min in group I and 14.38 ± 4.48 min in group II, which indicated that the recovery was faster in group I than in group II, but without statistical significance (P > 0.05). During the duration of neuromuscular blockade, 8 patients had T₁ < 3%, 4 T₁ of 3%–7% and 3 T₁ of 7%–10% in group I; T₁ was maintained between 0 and 20% in group II.ConclusionsAlthough cisatracurium consumption was significantly lower in continuous infusion than in intermittent bolus injection, continuous infusion can obtain more stable neuromuscular blockade than intermittent bolus injection.     

Nalbuphine by PCA-pump for analgesia following hysterectomy: bolus application versus continuous infusion with bolus application.

The analgesic properties of the partial agonist-antagonist nalbuphine in the postoperative period are well known. When used for patient-controlled analgesia (PCA) the effectiveness of this substance is comparable to that of morphine or tramadol. However, the optimal programme for administration of nalbuphine in PCA-pumps has not been investigated. In particular, the combination of bolus administration vs bolus administration plus continuous basal administration is disputable.We hypothesized that the administration of an extra basal rate of nalbuphine in addition to the patient- triggered bolus administration and supplemental doses of diclofenac when required, would lead to a significant improvement in analgesia, without affecting the differences in vital signs and side effects.After approvement by the institutional ethics committee, 50 female patients (ASA I or II) scheduled for elective hysterectomy were included in a prospective, single-blinded study and randomized either into bolus-continuous (BC-)group (3 mg base rate/h, 1 mg bolus, 20 min lock out) or bolus (B-)group (no base rate, 1 mg bolus, 10 min lock out). During the observation period (up to 24 h postoperative) vital parameters, extent of analgesia (10-step VAS), and vigilance (5-step scale) were registered. Groups were compared by using unpaired Student t-test. A p<0.05 was considered to be significant.No differences were found in demographic data or vital parameters (MAP, PaO2, PaCO2, respiratory rate, heart rate, peripheral SaO2) during the observation period. Vital parameters showed no pathological changes in any group. With an identical rate of requirement for diclofenac (32 and 36%), analgesia in BC-group showed a decrease in VAS from 4.28+/-2.11 to 2.04+/-1.21 and from 3.64+/-2.20 to 2.08+/-0.96 in B-group. Vigilance was only marginally diminished in both groups. No serious side effects were found in either group. The consumption of nalbuphine (mg) was significantly higher in BC-group (70.28+/-13.85 vs. 47.44+/-22.99;p =0.0002) when compared to B-group. Subjective rating of effectiveness by the patients was similar in both groups.The two administration settings of nalbuphine by PCA pump have shown to be equally effective in the treatment of postoperative pain following hysterectomy. However, as the total amount of nalbuphine was significantly lower in B-group, the use of this administration schedule should be encouraged.     

Design flaw can convert commercially available continuous syringe pumps to intermittent bolus injectors

Objective: To investigate if unexpected behaviour of neonatal and paediatric patients connected to syringe pumps could be explained by transient elevation of these devices. Design: Five different commercially available syringe pumps were set at an infusion rate of 1 ml/h and then subjected to a vertical displacement manoeuvre (height 1 m). The actual delivered infusion volumes in association with the displacement manoeuvre were measured by a high precision weight scale connected to a computer. Setting: A medical technology laboratory in a university hospital. Measurements and results: Elevation of the devices resulted in a rapid bolus injection of 0.19–2.28 ml. Returning the devices to their original positions resulted in an aspiration into the system of 0.06–0.34 ml. The times both for bolus injection and for aspiration into the system were less than 1 min in all cases. The up-down manoeuvre was followed by a period with zero infusion ranging from 8 to 105 min. Conclusions: Design flaws in the construction of syringe pumps can expose patients to substantial danger following vertical displacemet if potent drugs are being infused. If potent drugs are infused, care should be taken not to change the vertical position of the syringe pump even for short periods of time. Before buying new equipment, the authors recommend that the delivery characteristics of these devices should not only be tested during ordinary bench testing but should also include the reaction to a vertical displacement manoeuvre. Received: 6 June 1997 Accepted: 8 July 1997     

Albumin bolus administration versus continuous infusion in critically ill hypoalbuminemic pediatric patients

Objective To test the hypothesis that the rate of degradation of exogenously administered albumin is fater with bolus administration that with continuous infusion and thus that a bolus administration is less efficacious in restoring blood albumin concentration (BAC) in the hypoalbuminemic critically ill pediatric patient.Design A prospective, controlled study of two groups of patients.Setting Pediatric intensive care unit (PICU) of a children's hospital.Patients 37 cirtically ill hypoalbuminemic patients. (BAC2.8 g/dl), in whom no overt protein-losing disease was identified, were divided into two treatment groups and included in a 60-h study.Interventions 18 patients were given an i.v. bolus of 1 g/kg of 25% albumin over 4 h. This treatment was repeated after 24 and 48 h. Nineteen other patients were given the same dose of 1 g/kg of 25% albumin as a continuous 24-h infusion throughout the 60-h study period. BAC along with sodium, potassium, and total and ionized calcium were measured in the serum of blood samples obtained at predetermined intervals.Measurement and main results A 4 h bolus of albumin resulted in an acute rise in BAC, which declined to baseline within 24 h. A continuous infusion resulted in a steady rise in BAC with 24-h levels significantly higher than baseline. The percent change in mean BAC from baseline, calculated at 12-h intervals during the 60-h study period, showed a steady increase in the continuous infusion group with a 34% increase after the first 24 h. In contrast, the 4-h bolus method resulted in major fluctuations in the BAC values with only a 14% increase (p<0.05) after 24 h. Albumin's volume of distribution, half-life and elimination constant, calculated based on blood albumin values during the first 24 h after the bolus administration, were 0.12±0.03 1/kg, 4.6±1.8 h and 0.17±0.06 h^–1, respectively. This half-life did not apply to the continuous infusion group as a steady state was not achieved after 30 h (6 half-lives), and BAC continued to rise throughout the 60-h study period. No significant changes in blood electrolytes were observed with either method.Conclusions The half-life of exogenous albumin in the critically ill hypoalbuminemic pediatric patient is short if given as a bolus. Continuous infusion therapy appears to be more efficacious in increasing BAC over time, as the half-life with this method appears to be longer.An abstract of this paper was presented at the SCCM meeting in Orlando, Florida in February 1994.     

Glucose control in the medical patient: bolus insulin dosing compared to basal-bolus insulin dosing

With "Manifestations of Poor Glycemic Control" included in the Centers for Medicare and Medicaid Services (2010) present on-admission criteria, hospitals are at a pivotal point in needing to evaluate current methods and outcomes of glycemic management. This study provides one hospital's comparison of two methods of hyperglycemia management: basal insulin and basal-bolus insulin.     

In vivo efficacy of continuous infusion versus intermittent dosing of linezolid compared to vancomycin in a methicillin-resistant Staphylococcus aureus rabbit endocarditis model

Linezolid is the first drug issued from the oxazolidinones, a novel class of antimicrobial agents with potent activity against gram-positive pathogens. A rabbit endocarditis model was used to compare the in vivo activities of different linezolid regimens mimicking intermittent dosing of 10 mg/kg of body weight every 12 h for 5 days or continuous (constant-rate) infusion of a daily dose of 20 mg/kg (for 5 days) or 40 mg/kg (for 3 and 5 days) and the activities of intermittent dosing and continuous infusion of vancomycin (for 5 days). The in vivo activities of these regimens were tested against three strains of methicillin-resistant Staphylococcus aureus. A human-like pharmacokinetic simulation was used for linezolid in order to improve the extrapolation of the results to human therapy. All linezolid regimens significantly reduced the numbers of S. aureus cells in aortic valve vegetations compared to the numbers in the control groups. Linezolid intermittent dosing had an in vivo bacteriostatic effect. Switching from intermittent dosing to continuous infusion (at the same dose) led to in vivo bactericidal activity, with a decrease of at least 3 log(10) CFU/g of vegetation compared to the counts for the controls. After 5 days of treatment, continuous infusion of linezolid (corresponding to a daily dose of 40 mg/kg in humans) seemed to be at least as effective as vancomycin against the three strains. No resistant variant was isolated from the vegetations during any of the treatments. These data suggest that continuous infusion of linezolid could be an appropriate alternative to the use of glycopeptides for the treatment of severe methicillin-resistant S. aureus infections.     

早期间歇持续微量喂养在早产低出生体质量儿中的应用

目的探讨早期间歇持续微量喂养在早产低出生体质量儿(VLBMI)护理中的应用效果。方法选取84例VLBMI患儿采用随机字母表法分为对照组和观察组,各42例。对照组在出生24 h后行临床常规胃管喂养,观察组在出生24 h内行间歇持续微量喂养,对比2组患儿不耐受情况、体质量变化情况、达到完全肠道喂养所需时间、吸吮吞咽功能建立时间、黄疸消退时间以及住院时间。结果观察组患儿喂养不耐受发生率为7.14%,低于对照组的30.95%(P0.05);观察组患儿每日体质量增长量、达到完全肠道喂养所需时间、吸吮吞咽功能建立时间、黄疸消退时间、平均住院时间均优于对照组(P0.05)。结论在VLBMI患儿的临床治疗护理过程中实施早期间歇持续微量喂养,可有效改善患儿不耐受情况,促进体质量增长和肠道功能恢复,缩短住院时间。     

Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial

Introduction

Intravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF). We sought to determine if there are any differences in clinical outcomes between intravenous bolus and continuous infusion of loop diuretics.

Methods

Subjects with ADHF within 12 hours of hospital admission were randomly assigned to continuous infusion or twice daily bolus therapy with furosemide. There were three co-primary endpoints assessed from admission to discharge: the mean paired changes in serum creatinine, estimated glomerular filtration rate (eGFR), and reduction in B-type natriuretic peptide (BNP). Secondary endpoints included the rate of acute kidney injury (AKI), change in body weight and six months follow-up evaluation after discharge.

Results

A total of 43 received a continuous infusion and 39 were assigned to bolus treatment. At discharge, the mean change in serum creatinine was higher (+0.8 ± 0.4 versus -0.8 ± 0.3 mg/dl P <0.01), and eGFR was lower (-9 ± 7 versus +5 ± 6 ml/min/1.73 m²P <0.05) in the continuous arm. There was no significant difference in the degree of weight loss (-4.1 ± 1.9 versus -3.5 ± 2.4 kg P = 0.23). The continuous infusion arm had a greater reduction in BNP over the hospital course, (-576 ± 655 versus -181 ± 527 pg/ml P = 0.02). The rates of AKI were comparable (22% and 15% P = 0.3) between the two groups. There was more frequent use of hypertonic saline solutions for hyponatremia (33% versus 18% P <0.01), intravenous dopamine infusions (35% versus 23% P = 0.02), and the hospital length of stay was longer in the continuous infusion group (14. 3 ± 5 versus 11.5 ± 4 days, P <0.03). At 6 months there were higher rates of re-admission or death in the continuous infusion group, 58% versus 23%, (P = 0.001) and this mode of treatment independently associated with this outcome after adjusting for baseline and intermediate variables (adjusted hazard ratio = 2.57, 95% confidence interval, 1.01 to 6.58 P = 0.04).

Conclusions

In the setting of ADHF, continuous infusion of loop diuretics resulted in greater reductions in BNP from admission to discharge. However, this appeared to occur at the consequence of worsened renal filtration function, use of additional treatment, and higher rates of rehospitalization or death at six months.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01441245","term_id":"NCT01441245"}}NCT01441245. Registered 23 September 2011.     

Intravenous bolus of ultra-low-dose naloxone added to morphine does not enhance analgesia in emergency department patients.

There is some evidence from in vitro, animal, and postoperative clinical studies that low doses of opioid antagonists combined with morphine increase analgesia. The theoretical model of this effect posits that ultra-low doses of opioid antagonists selectively antagonize excitatory, but not inhibitory, opioid receptor-mediated signaling. To determine whether this effect occurs in emergency department patients presenting with severe acute pain, we conducted a randomized, double-blind placebo-controlled trial to assess the relative analgesic effect of morphine administered with 3 different doses of naloxone versus morphine alone. Patients received 0.1 mg/kg morphine intravenously (IV) over 2 min plus one of 3 different doses of naloxone (0.1 ng/kg, 0.01 ng/kg, or 0.001 ng/kg) or normal saline. A 0 to 10 numerical rating scale (NRS) was used to measure pain intensity at baseline and every 30 min up to 4 hours. One hundred fifty-six patients with a median NRS of 10 (IQR: 8-10) were studied. There were no clinically or statistically significant differences in the mean pain intensity of patients in the 4 treatment groups over the 4-hour study period, nor were there differences in the administration of additional analgesics or incidence of side effects. PERSPECTIVE: Ultra-low doses of naloxone in the 0.001 ng/kg to 0.1 ng/kg range do not enhance the analgesia provided by morphine alone among emergency department patients with acute, severe pain. This suggests that naloxone in these doses is not an effective adjunct to morphine for control of acute pain.     

Serum bactericidal activity of ceftazidime: continuous infusion versus intermittent injections.

Since beta-lactam antibiotics have concentration-independent killing, bacterial eradication is a function of the time the serum drug concentration remains above the drug's MIC (T > MIC). We compared the serum bactericidal titers (SBTs) of ceftazidime given by continuous infusion (CI) or by intermittent bolus dosing (BD) against two clinical isolates each of Pseudomonas aeruginosa and Escherichia coli to determine if CI would allow lower daily dosing while still providing equal bactericidal activity compared with BD. This was an open-labeled, randomized, steady-state, four-way crossover study with 12 healthy volunteers. The ceftazidime regimens were 1 g every 8 h (q8h) BD, 1 g q12h BD, 3 g over 24 h CI, and 2 g over 24 h CI. The areas under the bactericidal curves were calculated by the trapezoidal rule using the reciprocal of the SBT. For all organisms the areas under the bactericidal curves for intermittent versus the CI regimens were the same for equal doses (P > 0.05). For both strains of E. coli all four regimens provided SBTs of > or = 1:2 over the dosing interval and 100% T > MIC. The 1-g q8h BD and q12h BD regimens provided T > MIC of 82 and 52%, respectively, for both P. aeruginosa isolates (MICs, 4 micrograms/ml). In comparison, the 2- and 3-g CI regimens always maintained SBTs of > or = 1:2 and T > MIC over the 24-h period as serum drug concentrations were 12.8 +/- 3.0 and 18.2 +/- 4.5 micrograms/ml, respectively. CI optimizes the pharmacodynamic and pharmacoeconomic profile of ceftazidime by providing adequate antibacterial activity over the 24-h dosing period with a reduction in the total daily dose of the antimicrobial agent.