The impact of continuous haemofiltration with high-volume fluid exchange during cardiopulmonary bypass surgery on the recovery of patients with impaired renal function: a pilot randomised trial.

BACKGROUND: There is widespread variability in clinical practice within cardiac surgery units worldwide on the use of haemofiltration. The clinical impact and safety of this modality is, however, unknown. OBJECTIVES: The primary pilot trial objectives were as follows: to assess the feasibility of randomising 60 patients with impaired kidney function undergoing on-pump coronary artery bypass graft (CABG) surgery within 6 months; to assess the suitability and reliability of our chosen outcome measures; to explore issues that may impact on recruitment into a definitive trial; and to undertake an exploratory economic evaluation. DESIGN: A pilot, single-centre, open-label randomised trial. SETTING: Liverpool Heart and Chest Hospital NHS Foundation Trust between November 2010 and March 2012. PARTICIPANTS: Men and women, aged > 18 years of age, undergoing on-pump CABG surgery, who had pre-operative impaired kidney function indicated by an estimated glomerular filtration rate (eGFR) of < 60 ml/minute adjusted for 1.73 m(2) of body surface area. INTERVENTIONS: Group 1: patients who received haemofiltration during bypass (experimental group). Group 2: patients who did not receive haemofiltration during bypass (control group). MAIN OUTCOME MEASURES: (1) Feasibility outcome measures: barriers to recruitment to a larger trial were documented as observations made during the recruitment period of the trial. Reliability of data collection methods was monitored using a 13-point case record form validation check for data entry against the patient clinical notes and the trial database. (2) The main clinical outcomes were frequency of intensive care unit (ICU) stay of duration > 3 days and the length of ICU stay days. (3) Other clinical outcomes were the need for postoperative haemofiltration in the ICU, mechanical ventilation time, hospital stay, composite of outcome of unfavourable perioperative events and eGFR values at 6 weeks' follow-up. (4) Secondary health economic feasibility outcomes. RESULTS: Recruitment into the pilot trial was from 21 November 2010 to 30 March 2012. Thirty-seven eligible patients were consented and successfully randomised into the trial arms (30%). The main issues impacting on recruitment were the high volume of off-pump CABG surgery within the centre; recruitment being restricted to research nurses' working hours of the week; issues arising associated with the screening process for identifying prospective eligible patients based on eGFR values; protocol deviations/treatment crossovers; and unexpected outbreaks of pandemic influenza and other infectious conditions. The data collection process was sufficiently robust, with few errors detected. The length of ICU stay days was deemed a suitable primary outcome. There was an overall trend towards reduction in the length of ICU stay for patients who were given intraoperative haemofiltration, more so for those with diabetes. The economic evaluation estimated that the incremental costs per person were £1744 lower for the intraoperative haemofiltration group, while the incremental benefits per person increased by 0.11. CONCLUSION: Given sufficient resources and broadening of the inclusion criteria, the recruitment into a larger multicentre trial is feasible and may demonstrate potential clinical and cost benefits of using intraoperative haemofiltration in this group of patients. However, owing to the small sample size in this pilot trial, no firm conclusions can be drawn from the findings at this stage. The outcomes of this pilot study are very encouraging and suggest that it is feasible to design a continuous superiority trial with the length of ICU stay days or time to tracheal extubation as the primary outcome measure, provided that guidelines for avoiding bias are implemented. An alternative primary outcome measure that avoids bias is mortality. The inclusion criteria should also be widened to include all cardiac surgery patients with impaired renal function. TRIAL REGISTRATION: ISRCTN49513454. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 49. See the HTA programme website for further project information.

A pilot randomised controlled trial in intensive care patients comparing 7 days' treatment with empirical antibiotics with 2 days' treatment for hospital-acquired infection of unknown origin.

BACKGROUND: Management of cardiac intensive care unit (ICU) sepsis is complicated by the high incidence of systemic inflammatory response syndrome, which mimics sepsis but without an infective cause. This pilot randomised trial investigated whether or not, in the ICU, 48 hours of broad-spectrum antibiotic treatment was adequate to safely treat suspected sepsis of unknown and unproven origin and also the predictive power of newer biomarkers of sepsis. OBJECTIVE: The main objective of this pilot study was to provide preliminary data on the likely safety and efficacy of a reduced course of antibiotics for the treatment of ICU infections of unknown origin. DESIGN: A pilot, single-centre, open-label randomised trial. SETTING: This study was carried out in the ICU of a tertiary heart and chest hospital. PARTICIPANTS: Patients being treated within the ICU were recruited into the trial if the intensivist was planning to commence antibiotics because of evidence of systemic inflammatory response syndrome and a strong suspicion of infection but there was no actual known source for that infection. INTERVENTIONS: Broad-spectrum antibiotic treatment administered for 48 hours (experimental) compared with treatment for 7 days (control). MAIN OUTCOME MEASURES: The primary outcome was a composite outcome of the rate of death or initiation of antibiotic therapy after the completion of the treatment schedule allocated at randomisation. Secondary outcomes included the duration of mechanical ventilation and ICU and hospital stay; the incidence of infection with Clostridium difficile (B. S. Weeks & E. Alcamo) Jones & Bartlett International Publishers, 2008, or methicillin-resistant Staphylococcus aureus (MRSA) (B. S. Weeks & E. Alcamo) Jones & Bartlett International Publishers, 2008; resource utilisation and costs associated with each of the two pilot arms; the ratio of patients screened to patients eligible to patients randomised; the incidence of crossover between groups; and the significance of newer biomarkers for sepsis for predicting patients' need for further antibiotics. RESULTS: A total of 46 patients were recruited into the trial, with 23 randomised to each group. There was no significant difference between the two groups in terms of the composite primary outcome measure. The risk difference was 0.12 [95% confidence interval (CI) 0.11 to 0.13; p = 0.3]. In the 2-day group, four patients (17.4%) required further antibiotics compared with three (13%) in the 7-day group. Four patients died within the trial period and the deaths were not trial related. Patients who died during the trial period received no additional antibiotics in excess of their trial allocation. There were no documented incidences of MRSA or C. difficile infection in either group. No significant differences in adverse events were observed between the groups. Key economic findings were mean antibiotic costs per patient of £168.97 for the 2-day group and £375.86 for the 7-day group. The potential per annum cost saving for the ICU of 2-day treatment was estimated to range from £108,140 to £126,060. Patient screening was considered the biggest barrier to recruitment. There was no crossover between the two randomised groups. Data verification ascertained > 98% accuracy in data collection. Baseline procalcitonin was found to be predictive of the composite outcome (death and needing further antibiotics) (odds ratio 1.79, 95% CI 1.20 to 2.67; p = 0.005). Analysis of baseline procalcitonin also indicated a trend towards it being a predictor of restarting antibiotics, with an odds ratio of 1.45 (95% CI 1.04 to 2.02; p = 0.01). CONCLUSIONS: Data from this pilot study suggest that there could be significant benefits of reducing broad-spectrum antibiotic use in the ICU without it undermining patient safety, with a potential cost saving in our unit of over £100,000 per year. Evidence from this pilot trial is not definitive but warrants further investigation using a large randomised controlled trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN82694288. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 36. See the HTA programme website for further project information.

Double-blind comparison of intrapleural saline and 0.25% bupivacaine for ipsilateral shoulder pain after thoracotomy in patients receiving thoracic epidural analgesia.

BACKGROUND: The aim of this prospective double-blind randomized placebo-controlled study was to investigate the effect of intrapleural bupivacaine on ipsilateral post-thoracotomy shoulder pain in patients receiving thoracic epidural analgesia. METHODS: Of the 68 patients recruited to the study, 41(60%) developed ipsilateral shoulder pain within 2 h of surgery. These patients were randomly assigned to receive either 40 ml of intrapleural bupivacaine 0.25% with epinephrine 1:200 000 or 40 ml of intrapleural saline. The study solution was injected into the tube of a basal drain that had been clamped distal to the site of administration. Shoulder pain at rest and on coughing was assessed using a visual analogue scale (VAS) and an observer verbal rating score (OVRS) immediately before and 30 min, 1 h, 2 h, 3 h and 4 h after intrapleural bupivacaine/saline. The total volume of epidural solution administered was recorded. RESULTS: Thirty-nine patients completed the study and were included in the analysis. There were no significant differences in baseline characteristics between the two groups. There were no significant differences between groups for VAS or OVRS pain scores at rest or with cough at any of the six assessment times. The total volumes of epidural solution administered to the bupivacaine and saline groups were 56 ml and 48 ml, respectively. This difference was not significant. CONCLUSION: Intrapleural administration of 40 ml of bupivacaine 0.25% does not provide effective pain relief for ipsilateral post-thoracotomy shoulder pain.

A prospective, randomised, single-blind pilot study to determine the effect of anaesthetic technique on troponin T release after off-pump coronary artery surgery.

Ischaemic damage to the myocardium inevitably occurs during coronary artery surgery. However, the extent of the damage may be influenced by the anaesthetic technique used. The most sensitive and reliable marker of myocardial damage is currently thought to be troponin T. We conducted a prospective, randomised, single-blind pilot study to determine the baseline values of troponin T release after off-pump coronary artery bypass surgery in 30 patients randomly allocated to receive either propofol, isoflurane or isoflurane and high thoracic epidural analgesia. All other treatment was standardised. Patients undergoing emergency surgery and those with unstable angina were excluded. Blood samples were taken at 0, 3, 6, 12, 24 and 48 h after surgery for troponin T analysis. Mean troponin T levels at 24 h were not significantly different between the groups (p = 0.41). These data allows appropriate power calculations for further, large-scale studies to determine the anaesthetic technique that provides optimal myocardial protection.

Optimal concentration of epidural fentanyl in bupivacaine 0.1% after thoracotomy.

BACKGROUND: The aim of this prospective, double-blind, randomized controlled trial was to investigate the analgesic and adverse effects of three commonly used concentrations of thoracic epidural fentanyl with bupivacaine in patients undergoing thoracotomy for lung resection. METHODS: We studied 99 patients who were randomized to receive fentanyl 2 microg ml(-1) (group 2), fentanyl 5 microg ml(-1) (group 5) and fentanyl 10 microg ml(-1) (group 10) in bupivacaine 0.1% via a thoracic epidural. Postoperatively, pain on coughing was assessed using a visual analogue scale (VAS) and an observer verbal rating score (OVRS) at 2, 8, 16 and 24 h. At the same times, sedation, pruritus and nausea were assessed. RESULTS: Of 29, 28 and 32 patients who completed the study in groups 2, 5 and 10 respectively, there was no significant difference in baseline characteristics between the three groups. The number of patients with episodes of unsatisfactory pain, i.e. VAS scores >30 mm and OVRS >1, at each of the four assessments postoperatively was significantly (P<0.01) higher in group 2 than in groups 5 and 10. In group 10, 16 patients had sedation scores >1 compared with 10 each in groups 2 and 5. In addition, 19 patients in group 10 experienced pruritus compared with 12 each, in groups 2 and 5. These differences were not significant. Nausea was not significantly different between the three groups. CONCLUSION: We conclude that thoracic epidural fentanyl 5 microg ml(-1) with bupivacaine 0.1% provides the optimum balance between pain relief and side effects following thoracotomy.

Gastric emptying in post-thoracotomy patients receiving a thoracic fentanyl-bupivacaine epidural infusion.

BACKGROUND AND OBJECTIVE: The effect of anaesthesia and surgery on gastric emptying is not constant, and this has not been previously studied in patients undergoing thoracotomy for lung resection with a bupivacaine-fentanyl epidural infusion for analgesia. There are important implications in this group of patients with regards to the recommencement of important oral medication as well as the risks of aspiration of gastric contents. The study examined gastric emptying in these patients until the second postoperative day. METHODS: In a prospective repeated measures study, the effect of fentanyl-bupivacaine epidural analgesia at the mid-thoracic level on gastric emptying was assessed in 11 patients undergoing thoracotomy for lung resection. Gastric emptying was measured using a paracetamol absorption technique. Patients acted as their preoperative controls and were assessed 4 h postoperatively and on the second postoperative day. RESULTS: The mean (SEM) maximum plasma paracetamol concentration was 204.6 (20.4) micromol L(-1) before operation, 61 (9.5) micromol L(-1) 4 h postoperatively and 114.3 (22.6) micromol L(-1) on the second postoperative day. Mean (SEM) paracetamol absorption at 120 min was 15,638 (1441) micromol min L(-1) preoperatively, 5731 (821) micromol min L(-1) 4 h postoperatively and 9325 (1759) micromol min L(-1) on the second postoperative day. Postoperative values were significantly (P < 0.005) less than the preoperative values. CONCLUSIONS: After thoracotomy, gastric emptying was delayed until at least the second postoperative day in patients receiving mid-thoracic fentanyl-bupivacaine epidural analgesia.

Ipsilateral shoulder pain after thoracotomy with epidural analgesia: the influence of phrenic nerve infiltration with lidocaine.

UNLABELLED: Patients receiving effective thoracic epidural analgesia for postthoracotomy pain may still complain of severe ipsilateral shoulder pain. The etiology of this pain is unclear. In this randomized, double-blinded, placebo-controlled study, we investigated the effect of phrenic nerve infiltration with lidocaine or saline on postoperative shoulder pain in 48 patients. After completion of a lung resection, patients received either 10 mL of 1% lidocaine or 10 mL of 0.9% saline infiltrated into the periphrenic fat pad at the level of the diaphragm. Shoulder pain was experienced by 33% of patients receiving lidocaine, compared with 85% of patients receiving saline (P < 0.008). Overall pain scores were lower with lidocaine (P < 0.05). PaCO(2) values were not significantly higher with lidocaine in the first 2 h. We conclude that pain transmitted via the phrenic nerve and referred to the shoulder is the most likely explanation for the ipsilateral shoulder pain experienced by patients receiving epidural analgesia for postthoracotomy pain. IMPLICATIONS: Ipsilateral shoulder pain after thoracotomy is common and may be severe, even in the presence of a functioning thoracic epidural. We have shown that infiltration of the phrenic nerve with local anesthetic significantly and safely reduces this shoulder pain, potentially allowing the ideal goal of a pain-free thoracotomy.