Intermittent Bolus Doses Research Articles

Bolus Intravenous Procainamide in Patients with Frequent Ventricular Ectopics during Cardiac Magnetic Resonance Scanning: A Way to Ensure High Quality Imaging.

Acquiring high-quality cardiac magnetic resonance (CMR) images in patients with frequent ventricular arrhythmias remains a challenge. We examined the safety and efficacy of procainamide when administered on the scanner table prior to CMR scanning to suppress ventricular ectopy and acquire high-quality images. Fifty consecutive patients (age 53.0 [42.0–58.0]; 52% female, left ventricular ejection fraction 55 ± 9%) were scanned in a 1.5 T scanner using a standard cardiac protocol. Procainamide was administered at intermittent intravenous bolus doses of 50 mg every minute until suppression of the ectopics or a maximum dose of 10 mg/kg. The average dose of procainamide was 567 ± 197 mg. Procainamide successfully suppressed premature ventricular contractions (PVCs) in 82% of patients, resulting in high-quality images. The baseline blood pressure (BP) was mildly reduced (mean change systolic BP −12 ± 9 mmHg; diastolic BP −4 ± 9 mmHg), while the baseline heart rate (HR) remained relatively unchanged (mean HR change −1 ± 6 bpm). None of the patients developed proarrhythmic changes. Bolus intravenous administration of procainamide prior to CMR scanning is a safe and effective alternative approach for suppressing PVCs and acquiring high-quality images in patients with frequent PVCs and normal or only mildly reduced systolic function.

Comparison of two different methods for labor analgesia depending on the mode of epidural infusion administration (continuous or intermittent)

Introduction: The use of a local anesthetic solution with opioids as a continuous epidural infusion administration during labor is controversial. It is considered to prolong the second stage of labor and to increase the total delivered dose of anesthetic, without improving the analgesia in comparison with the usage of the same solution in intermittent bolus doses, periodically. This study is designed to compare these two techniques. Materials and methods: In this study, 60 parturient women were included. Labor analgesia started with a single bolus dose of 10 mL ropivacaine 0.1% administered epidurally in both groups. Group A was, subsequently, given epidurally Ropivacaine 0.15% with Fentanyl 2 μgr/mL in continuous infusion with a rate of 10 mL/h throughout labor, while Group B was given the same dose per hour but in two bolus doses of 5 mL administered every 30 min. In both groups, we had the possibility of additional bolus doses of 5 mL of the same solution with a lock out interval of 20 min. The total dosage received, the duration of the 2nd stage of labor, the method of delivery (assisted or not, Cesarean section), the motor activity (using the Bromage scale) and the pain intensity (using the VAS 1–10, every 20 min) were evaluated. Results: No statistically significant differences were observed in the duration of labor (one way ANOVA), in the Bromage score and in the method of delivery between the two groups (x2 test). No differences were also observed in the recordings of pain intensity between the two groups (two-way ANOVA for repeated measurements), but in some specific instances Group A presented higher VAS score, although the total dosage of local anesthetic received was greater in this group compared to group B (180 mL vs. 162 mL, p = 0.04). Conclusions: The use of intermittent epidural bolus doses compared to a continuous infusion technique is associated with lower total consumption and periodically better pain management.

A randomized, double-blinded comparative study of phenylephrine infusion and norepinephrine infusion for the prevention and treatment of spinal anesthesia-induced hypotension in elective and emergency cesarean deliveries

Context and Aims: Among vasopressors used to treat postspinal hypotension (PSH) in cesarean sections (CS), phenylephrine (PE) is the preferred drug at present but reflex bradycardia and thus reduction in cardiac output still pose a concern. Norepinephrine (NE), with its better pharmacological properties, may be a better alternative to overcome this risk. Hence, we did this study intending to compare both the drugs. Materials and Methods: A double-blinded, randomized, controlled trial (RCT) was carried out on 70 patients, 35 in each group-group P (PE) and group N (NE) undergoing CS, to compare and evaluate the efficacy of both drugs for preventing and treating PSH. Patients in Group P and Group N were given intravenous infusion of PE at the rate of 50 μg/min and NE at the rate of 2.5 μg/min, respectively, after the intrathecal injection of bupivacaine. The number of intermittent bolus doses required, heart rate, and mean arterial pressure (MAP) at predefined intervals were noted. Results: The incidence of hypotension calculated from the number of bolus doses required was lower in Group N than in Group P for the initial 15 min (P Conclusion: This study suggests that NE infusion is superior to PE infusion when used in the potency ratio of 20:1, to prevent and treat PSH in CS, with a lesser number of side effects.

Pre-procedure intravenous lidocaine administration on propofol consumption for endoscopic retrograde cholangiopancreatography: A prospective, randomized, double-blind study.

The endoscopic retrograde cholangiopancreatography (ERCP) procedure is generally performed in patients with high comorbidity. We aimed to reduce the consumption of propofol by adding lidocaine before ERCP. Eighty ERCP patients with ASA I-III, aged between 45-75years, were randomly divided into two groups. Lidocaine group (group L, n=40), received 1-mg midazolam, 1.5mg/kg lidocaine, and 1mg/kg propofol intravenously. The control group (group C, n=40) received 1-mg midazolam, saline in the same volume as the lidocaine group, and 1mg/kg propofol intravenously. Propofol was administered with intermittent bolus doses. Propofol consumption, oropharyngeal reflex, recovery time, endoscopist satisfaction, ketamine need, and side-effects were recorded. Propofol consumption during the procedure was statistically lower in group L than in the control group (157.25±39.16mg vs 228.75±64.62mg respectively, P<0.001). Additionally, recovery time was statistically faster in group L compared with the control group (7.78±3.95min vs 11.92±3.24min respectively, P<0.001). The oropharyngeal reflex was less in group L than control group (6/40 vs 15/40 respectively, P=0.042). There was no significant difference between the two groups regarding visual analogue scale scores and endoscopist satisfaction (P>0.05). We recommend the use of intravenous lidocaine before the ERCP procedure as it reduces propofol consumption, recovery times, and oropharyngeal reflex.

Does Programmed Intermittent Epidural Bolus Improve Childbirth Conditions of Nulliparous Women Compared With Patient-controlled Epidural Analgesia? A Multicentre, Randomized, Controlled, Triple-blind Study

(Eur J Anaesthesiol. 2019;36:755–762) Currently about 80% of deliveries in France involve an epidural for labor analgesia. Epidural rates and programs have changed over time, but various authors have found that a programmed intermittent epidural bolus (PIEB) plus patient-controlled epidural analgesia (PCEA) demand dosing strategy for maintenance of labor analgesia decreased the rate of instrumental vaginal delivery, lessened anesthetic drug consumption and increased maternal satisfaction scores compared with a continuous background infusion+PCEA. This study aimed to investigate whether the use of a modern PIEB pump improved the mechanics of the second stage of labor compared with a conventional epidural analgesia technique.

Continuous intravenous versus intermittent bolus midazolam with remifentanil during arteriovenous fistula placement with monitored anesthesia care in chronic renal failure patients: a randomized controlled trial.

ABSTRACTBACKGROUND: There is limited data on the use of intravenous continuous infusion (CI) versus intravenous intermittent bolus (IB) doses of midazolam for conscious sedation in patients with chronic renal failure. Unexpected adverse events can occur in chronic renal failure patients undergoing short procedures.OBJECTIVE: Investigate and compare the sedoanalgesic and adverse effects of intravenous continuous infusion (CI) use of midazolam with intravenous intermittent bolus (IB) doses of midazolam while using intravenous remifentanil as a rescue medication, and assess patient and surgeon satisfaction.DESIGN: Prospective, randomized, single-blind controlled study.SETTINGS: Two tertiary care hospitals.PATIENTS AND METHODS: Study included patients aged 43-81 years with a diagnosis of chronic renal failure who were referred for an arteriovenous fistula procedure with modified anesthesia care between August 2012 and April 2016. The patients were randomized to intravenous CI or IB doses of midazolam. IB doses of remifentanil were used as a rescue medication.MAIN OUTCOME MEASURES: Primary outcomes were amounts of midazolam and remifentanil medications during the operation, the amount of remifentanil as a rescue medication, and the satisfaction of patient and surgeon.SAMPLE SIZE: 116 assessed for eligibility; 99 randomized to CI (n=50) or IB doses (n=49 of midazolam).RESULTS: The total dose of midazolam by CI was greater than with midazolam by IB (P=.002). The total dose of remifentanil was higher with IB doses of midazolam in comparison to CI of midazolam (P=.001). The groups were similar in sedation and pain control, duration of procedure, recovery time, patient satisfaction and adverse events; surgeon satisfaction was greater with CI versus IB (P=.035).CONCLUSION: Intravenous CI midazolam during MAC provides better surgeon satisfaction then IB midazolam and can be used safely for arteriovenous fistula procedures.LIMITATIONS: Two different surgeon groups.CONFLICT OF INTEREST: None.

Systemic hemodynamic effects of norepinephrine versus phenylephrine in intermittent bolus doses during spinal anesthesia for cesarean delivery.

BackgroundNorepinephrine, a potent α-adrenergic agonist with β-adrenergic effects, has recently emerged as a potential alternative to phenylephrine that does not lower cardiac output (CO) and heart rate (HR) during cesarean deliveries. We examined the systemic hemodynamic effects of both agents in this setting, using intermittent bolus doses to treat spinal anesthesia-induced hypotension.MethodsA total of 56 parturients consenting to spinal anesthesia for elective cesarean delivery were randomly assigned to phenylephrine (100 μg/ml) or norepinephrine (5 μg/ml) intermittent bolus dosing. The primary study outcome was maternal normalized CO, examining and other hemodynamic variables, maternal side effects, and fetal outcomes secondarily.ResultsIn terms of systolic blood pressure and HR, there were significant within-group differences over time (P < 0.001 and P < 0.001, respectively). Normalized CO and stroke volume (SV) also showed significant differences between groups (P < 0.001 and P = 0.002, respectively). In the phenylephrine group, normalized CO and SV declined (relative to baseline values) by as much as 13% and 9%, respectively; whereas in the norepinephrine group, normalized CO did not differ significantly from baseline, and SV increased up to 5% (relative to baseline). Normalized total peripheral resistance likewise displayed significant within-group differences over time (P < 0.001).ConclusionsDuring elective cesarean delivery, intermittent bolus doses of norepinephrine proved effective for treating spinal anesthesia-induced hypotension, while maintaining CO and SV. No maternal complications or fetal effects were evident.

Side Effects of Intravenous Patient-Controlled Analgesia with Remifentanil Compared with Intermittent Epidural Bolus for Labour Analgesia - A Randomized Controlled Trial.

Epidural analgesia is considered a gold standard in obstetric anaesthesia and analgesia. However, in situation when it is contraindicated, unwanted by the patient or simply unavailable, remifentanil can be an excellent alternative. The goal of our study is to analyse the side effects of intravenous patient-controlled analgesia (IV PCA) with remifentanil compared with epidural analgesia during delivery. This study included 155 pregnant women in term for birth, divided into 2 groups: a remifentanil group (RG), and an epidural group (EG). Patients in the RG received intravenous PCA with remifentanil, while patients in the ЕG received epidural analgesia with programmed intermittent bolus dosing. Our primary outcome was maternal safety; the secondary outcome was neonatal safety. The results present a significantly lower SaO2 value of the parturients in the RG (96.95 ± 1.4 vs 98.22 ± 0.6), and a significantly higher respiratory rate per minute in the EG at all time points after the onset of analgesia (20.85 ± 1.4 vs 18.67 ± 0.9). There was more frequent sedation, nausea and vomiting in the RG, while in the EG there was a more elevated temperature, itching and irregularities in the CTG record. Regarding the newborn, there was no significant difference between the two groups in the Apgar scores, pH, pCO2, pO2, and bicarbonate, while there was a significantly lower value of the base excess in the RG group. PCA with remifentanil is safe for the mother, foetus and the newborn, with minimal side effects. Continuous respiratory monitoring, oxygen supply and following of all consensus recommendations are mandatory.

Effect of Maternal Postpartum and Infant Intermittent Vitamin D Supplementation on Infant Vitamin D Status: A Systematic Review and Meta-Analysis of Trials (P11-089-19)

ObjectivesTo determine the response of infant (≤ 1 year) circulating 25-hydroxyvitamin D (25(OH)D) to maternal postpartum or infant intermittent vitamin D supplementation in comparison to current recommendations of direct daily oral infant supplementation (400 IU/d). MethodsMEDLINE, MEDLINE In-Process, Embase, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched up to December 4th 2018. A systematic search of online trial registries for unpublished, ongoing, or planned trials was also completed. Risk of bias was assessed using the Cochrane Risk Assessment Tool. Meta-analysis was limited to trials with a control group of infants receiving 400 IU vitamin D/d. A weighted mean difference (WMD) and 95% confidence interval (CI) was generated using infant 25(OH)D as a continuous outcome. Random-effects models accounted for within- and between-study variability. Statistical heterogeneity was quantified with the I2 statistic. ResultsA total of 28 trials were included, representing data from all 6 World Health Organization world regions. Of the 25 trials that specified a calciferol form, the majority (88%) employed vitamin D3. Six trials (21%) had an overall low risk of bias. Six trials qualified for meta-analysis, stratified by maternal (n = 4) and infant (n = 2) administration. Maternal supplementation resulted in a modestly lower infant vitamin D status than daily infant supplementation (WMD =-7.3 nmol/L; 95% CI: -14.0 to -0.6; I2 = 37%, P = 0.17). Comparison of infant intermittent bolus dosing to daily supplementation was limited by a small sample size and substantial heterogeneity, resulting in a wide CI (WMD = 10.2 nmol/L; 95% CI: -42.9 to 63.3; I2 = 96%, P < 0.001). Safety outcomes, including effects on calcium homeostasis, were inconsistently reported. Four ongoing trials were identified as potential contributors to future reviews. ConclusionsEvidence to support the use of specific alternative maternal or infant regimens to substitute for current daily infant vitamin D supplementation is weak and inconsistent. Dose-ranging, adequately powered trials are required to establish the efficacy and safety of feasible alternative strategies to prevent infant vitamin D deficiency Funding SourcesSickKids C-GCH Growth and Development Fellowship.

Continuous infusion versus intermittent bolus doses of fentanyl for analgesia and sedation in neonates: an open-label randomised controlled trial

ObjectiveAdequate data on fentanyl pharmacokinetics in neonates are lacking. The study was performed to compare serum concentrations and clinical outcome between continuous infusion (CI) and intermittent bolus (IB) doses of...

R5 Continuous Infusion for Pain Control after Pediatric Cardiothoracic Surgery Associated with Longer Length of Stay

Subjects were patients aged 3 months-4 years post-cardiac surgery with a midline sternotomy incision and planned early extubation at Advocate Children's Hospital-Oak Lawn. Sixty subjects were randomized to receive either a continuous infusion of morphine and midazolam or normal saline. The infusion group received a continuous intravenous morphine infusion at 0.03 mg/kg/hr along with a midazolam drip at 0.03 mg/kg/hr. Morphine bolus doses were available at 0.05 mg/kg/dose every two hours and midazolam 0.05 mg/kg/dose every one hour. Additional doses available at the discretion of the treating team. The control group received a normal saline infusion and the same bolus dosing. Providers were blinded to the infusion, but not to the bolus doses. Both groups received acetaminophen and ketorolac. FLACC scores were recorded hourly and as needed. There was no difference in number of bolus medication received between groups (p=0.39 for morphine, p=0.8 for midazolam). The mean FLACC score was 1.58 in the bolus group and 1.34 in the infusion group (p=0.35). Total morphine dose given was higher in the infusion group (0.23 mg/kg versus 0.9 mg/kg, p<0.01). Total midazolam dose given was higher in the infusion group (0.18 mg/kg versus 0.9 mg/kg, p<0.01). The length of ICU stay (LOS) was longer in the infusion group (4.5 days versus 2.7, p=0.03). The total hospital LOS was also longer in the infusion group (8.4 days versus 4.9, p=0.03). The addition of a continuous infusion did not decrease the amount of intermittent bolus doses or improve FLACC scores. Subjects in the infusion group did receive a significantly higher total dosage of these medications. We speculate that these higher doses led to longer ICU and hospital lengths of stay. Based on these findings, use of continuous infusions should be discouraged as routine practice after pediatric cardiac surgery in this age group.

Pharmacokinetics and pharmacodynamic target attainment of ceftriaxone in adult severely ill sub-Saharan African patients: a population pharmacokinetic modelling study.

In sub-Saharan Africa (SSA), the highly albumin-bound β-lactam ceftriaxone is frequently used for the empirical treatment of severe bacterial infections. Systemic drug exposure of β-lactams can be altered in critically ill ICU patients, but pharmacokinetic and pharmacodynamic data for non-ICU SSA populations are lacking. We performed a population pharmacokinetic study in an adult hospital population in Mozambique, treated with ceftriaxone for presumptive severe bacterial infection from October 2014 to November 2015. Four blood samples per patient were collected for total ceftriaxone (CEFt) and unbound ceftriaxone (CEFu) concentration measurement. We developed a population pharmacokinetic model through non-linear mixed effect analysis and performed simulations for different patient variable, dosing and pharmacodynamic target scenarios. Eighty-eight participants yielded 277 CEFt and 276 CEFu concentrations. The median BMI was 18.9 kg/m2 and the median albumin concentration was 29 g/L. In a one-compartment model with non-linear protein binding, creatinine clearance was positively correlated with CEFu clearance. For microorganisms with an MIC of 1 mg/L, simulations demonstrated that with a 1 g twice-daily regimen and a 2 g once-daily regimen, 95.1% and 74.8% would have a CEFu concentration > MIC during half of the dosing interval (fT>MIC = 50%), respectively, whereas this was only 58.2% and 16.5% for the fT>MIC = 100% target. Severely ill adult non-ICU SSA patients may be at substantial risk for underexposure to CEFu during routine intermittent bolus dosing, especially when their renal function is intact.

Continuous infusion of vancomycin is superior to intermittent dosing in critically ill patients

Introduction: Vancomycin is traditionally administered via intermittent bolus dosing, however increasing evidence now suggests that administration via a continuous infusion may be advantageous in specific cohorts of patients. This has yet to be demonstrated in a critically ill Australian population.

Assessing Propylene Glycol Toxicity in Alcohol Withdrawal Patients Receiving Intravenous Benzodiazepines: A One-Compartment Pharmacokinetic Model.

While some case reports indicate that high doses of propylene glycol (PG) may result in metabolic acidosis, there has been no large-scale study that evaluatedthe risk of metabolic acidosis in patients receiving PG-containing benzodiazepines for acute alcohol withdrawal. This study was undertaken to evaluate the potential toxicity of PG in patients with acute alcohol withdrawal treated with intermittent intravenous bolus doses of diazepam and/or lorazepam. This is a retrospective case study using data collected from 18 randomly selected patients receiving one or both of these medications per a modified Clinical Institute Withdrawal Assessment for Alcohol (CIWA) Class 3 protocol. Plasma levels of PG were estimated using a one-compartment pharmacokinetic model. Only two patients had an elevated anion gap compared to their baseline value with one also experiencing a significant increase in serum creatinine. No increases in serum osmolarity were noted. Analysis showed that the benzodiazepine dose received was a good predictor of the estimated PG concentration (r=0.6), but was poorly correlated with the anion gap. No significant correlation was found with the creatinine clearance or serum creatinine. Patients receiving several daily doses were at higher risk of developing an anion gap (r=0.33), but the estimated maximum PG concentration did not correlate with the anion gap or serum concentration. It does not appear that intermittent bolus administration of intravenous benzodiazepines for alcohol withdrawal influenced renal function or anion gap regardless of number of administered doses, amount of PG received, or the estimated PG concentration.

СОЧЕТАННАЯ АНЕСТЕЗИЯ ПРИ РЕЗЕКЦИИ ЛЕГКИХ

In order to improve outcomes of surgical treatment of thoracic diseases, the peri-operative protection is to be constantly enhanced. Goal: to assess the effect of combined anesthesia with thoracic epidural analgesia in the peri-operative period on hemodynamics and respiratory exchange during radical pulmonary surgery. Subjects and methods. The prospective randomized study was performed aiming to assess the effect of various options of anesthesia in 46 patients who had planned radical pulmonary surgery. The patients were randomly divided into two groups. Group 1 (n = 23) had combined anesthesia. Analgesia was provided through segmental epidural block on the level of Th 4 ‒Th 5 by intermittent bolus dosing of 0.75% solution of ropivacaine (0.7-0.8 mg/kg) and fentanyl (1.3-1.5 mcg/kg), and during the surgery, the mixture of 0.02% solution of ropivacaine and fentanyl (4 mcg/kg) was continuously infused at the rate of 4-6 ml/h. In Group 2 (n = 23), analgesia was provided by infusions of fentanyl, epidural analgesia was used in the post-operative period as a component of multi-modal post-operative pain relief. In both groups, the cortical component was provided by the low-flow inhalation of sevoflurane under BIS monitoring. Pipecuronium bromide solution was intermittently administered in order to provide muscle relaxation. Conclusion. The positive impact on hemodynamics and respiratory exchange was observed when using combined anesthesia based on thoracic epidural analgesia and inhalation anesthesia with sevoflurane.

Failed Nerve Blocks: Prevention and Management

Failed Nerve Blocks: Prevention and Management

Pharmacokinetics and Pharmacodynamic Target Attainment of Benzylpenicillin in an Adult Severely Ill Sub-Saharan African Patient Population.

In intensive care (ICU) patients, systemic exposure of β-lactam antibiotics can be altered, and positive clinical outcome is associated with increasing fT > MIC ratios. In sub-Saharan African hospitals, benzylpenicillin (PEN) is frequently used for the empiric treatment of severe pneumococcal infections. Pharmacokinetic data for non-ICU hospitalized populations are lacking. We performed a population pharmacokinetic (PPK) study in an adult Mozambican hospital population treated intravenously with PEN from October 2014 through November 2015. Four blood samples/patient were collected for total PEN (PENt) and unbound PEN (PENu) concentration measurement. We developed a PPK model through nonlinear mixed-effects analysis and performed simulations for different patient variable, dosing, and pharmacodynamic target scenarios. One hundred twelve participants yielded 387 PENt and 53 PENu concentrations. The median body mass index was 18.3 (range, 10.5-31.3) kg/m2 and the median albumin concentration and creatinine clearance (CrCl) were 29 (range, 12-44) g/L and 80 (range, 3-195) mL/minute, respectively. In a 1-compartment model, CrCl was positively correlated with PENt clearance. For infections with a microorganism with a minimum inhibitory concentration (MIC) of 1 mg/L, simulations demonstrated that with 3 million IU (1.8 g) every 6 hours, 74.1% would have a PENu concentration greater than the MIC during half of the dosing interval (fT > MIC = 50%), whereas this was 24.8% for the fT > MIC = 100% target. For pathogens with an MIC of 0.06 mg/L, these percentages were 98.2% and 72.3%, respectively. Severely ill adult sub-Saharan African patients may be at high risk for underexposure to PENu during routine intermittent bolus dosing, especially when their renal function is intact and when infected with pathogens with intermediate susceptibility.

Establishing an anaesthetist-delivered propofol sedation service for advanced endoscopic procedures: implementing the RCA/BSG guidelines

BackgroundFollowing recommendations from the Royal College of Anaesthetists and the British Society of Gastroenterology, we report our results of propofol sedation for complex endoscopic procedures delivered by a single consultant...

Norepinephrine Intermittent Intravenous Boluses to Prevent Hypotension During Spinal Anesthesia for Cesarean Delivery: A Sequential Allocation Dose-Finding Study.

The use of phenylephrine as the first-line agent for prevention and treatment of maternal hypotension during cesarean delivery (CD) may reduce cardiac output, posing a theoretical risk to mother and fetus. Norepinephrine has been suggested as a potential alternative, because its β-adrenergic effects might result in greater heart rate and cardiac output than phenylephrine. The use of norepinephrine to prevent and treat hypotension during CD is new, and its use as a bolus has not been fully determined in this context. The purpose of this study was to determine the effective norepinephrine dose, when given as intermittent intravenous (IV) boluses, to prevent postspinal hypotension in 90% of women undergoing elective CD (ED90). This was a prospective, double-blind sequential allocation dose-finding study, using the biased coin up-and-down design. Forty-term pregnant women undergoing elective CD under spinal anesthesia received a set intermittent norepinephrine bolus of either 3, 4, 5, 6, 7, or 8 µg every time their systolic blood pressure (SBP) fell to below 100% of baseline. The primary outcome was the success of the norepinephrine regimen to maintain SBP at or above 80% of baseline, from induction of spinal anesthesia to delivery of the fetus. Secondary outcomes included nausea, vomiting, hypertension (SBP > 120% of baseline), bradycardia (<50 bpm), upper sensory level of anesthesia to ice cold and umbilical artery and vein blood gases. The ED90 and 95% confidence intervals (CIs) were estimated using both truncated Dixon and Mood and isotonic regression methods. The estimated ED90 of norepinephrine was 5.49 µg (95% CI, 5.15-5.83) using the truncated Dixon and Mood method and 5.80 µg (95% CI, 5.01-6.59) using the isotonic regression method. The use of intermittent IV norepinephrine boluses to prevent spinal-induced hypotension in elective CD seems feasible and was not observed to be associated with adverse outcomes. Practically, we suggest an ED90 dose of 6 µg. Further work is warranted to elucidate the comparative effects of intermittent IV bolus doses of phenylephrine and norepinephrine, in terms of efficacy and safety.

Prolonged administration of β-lactam antibiotics - a comprehensive review and critical appraisal.

Prolonged infusion of β-lactam antibiotics as either extended (over at least 2 hours) or continuous infusion is increasingly applied in intensive care units around the world in an attempt to optimise treatment with this most commonly used class of antibiotics, whose effectiveness is challenged by increasing resistance rates. The pharmacokinetics of β-lactam antibiotics in critically ill patients is profoundly altered secondary to an increased volume of distribution and the presence of altered renal function, including augmented renal clearance. This may lead to a significant decrease in plasma concentrations of β-lactam antibiotics. As a consequence, low pharmacokinetic/pharmacodynamic (PK/PD) target attainment, which is described as the percentage of time that the free drug concentration is maintained above the minimal inhibitory concentration (MIC) of the causative organism (fT>MIC), has been documented for β-lactam treatment in these patients when using standard intermittent bolus dosing, even for the most conservative target (50% fT>MIC). Prolonged infusion of β-lactams has consistently been shown to improve PK/PD target attainment, particularly in patients with severe infections. However, evidence regarding relevant patient outcomes is still limited. Whereas previous observational studies have suggested a clinical benefit of prolonged infusion, results from two recent randomised controlled trials of continuous infusion versus intermittent bolus administration of β-lactams are conflicting. In particular, the larger, double-blind placebo-controlled randomised controlled trial including 443 patients did not demonstrate any difference in clinical outcomes. We believe that a personalised approach is required to truly optimise β-lactam treatment in critically ill patients. This may include therapeutic drug monitoring with real-time adaptive feedback, rapid MIC determination and the use of antibiotic dosing software tools that incorporate patient parameters, dosing history, drug concentration and site of infection. Universal administration of β-lactam antibiotics as prolonged infusion, even if supported by therapeutic drug monitoring, is not yet ready for "prime time", as evidence for its clinical benefit is modest. There is a need for prospective randomised controlled trials that assess patient-centred outcomes (e.g. mortality) of a personalised approach in selected critically ill patients including prolonged infusion of β-lactams compared with the current standard of care.