Efficacy of bilateral catheter superficial parasternal intercostal plane blocks using programmed intermittent bolus for opioid-sparing postoperative analgesia in cardiac surgery with sternotomy: A randomized, double-blind, placebo-controlled trial.

STUDY OBJECTIVE: This study investigated whether catheter superficial parasternal intercostal plane (SPIP) blocks, using a programmed intermittent bolus (PIB) with ropivacaine, could reduce opioid consumption while delivering enhanced analgesia for a period exceeding 48 h following cardiac surgery involving sternotomy. DESIGN: A double-blind, prospective, randomized, placebo-controlled trial. SETTING: University-affiliated tertiary care hospital. PATIENTS: 60 patients aged 18 or older, scheduled for cardiac surgery via sternotomy. INTERVENTIONS: The patients were randomly assigned in a 1:1 ratio to either the ropivacaine or saline group. After surgery, patients received bilateral SPIP blocks for 48 h with 0.4% ropivacaine (20 mL per side) for induction, followed by bilateral SPIP catheters using PIB with 0.2% ropivacaine (8 mL/side, interspersed with a 2-h interval) or 0.9% normal saline following the same administration schedule. All patients were administered patient-controlled analgesia with hydromorphone. MEASUREMENTS: The primary outcome was the cumulative morphine equivalent consumption during the initial 48 h after the surgery. Secondary outcomes included postoperative pain assessment using the Numeric Rating Scale (NRS) at rest and during coughing at designated intervals for three days post-extubation. Furthermore, recovery indicators and ropivacaine plasma levels were diligently documented. MAIN RESULTS: Cumulative morphine consumption within 48 h in ropivacaine group decreased significantly compared to saline group (25.34 ± 31.1 mg vs 76.28 ± 77.2 mg, respectively; 95% CI, -81.9 to -20.0, P = 0.002). The ropivacaine group also reported lower NRS scores at all recorded time points (P < 0.05) and a lower incidence of nausea and vomiting than the saline group (3/29 vs 12/29, respectively; P = 0.007). Additionally, the ropivacaine group showed significant improvements in ambulation (P = 0.018), respiratory exercises (P = 0.006), and self-reported analgesia satisfaction compared to the saline group (P = 0.016). CONCLUSIONS: Bilateral catheter SPIP blocks using PIB with ropivacaine reduced opioid consumption over 48 h, concurrently delivering superior postoperative analgesia in adult cardiac surgery with sternotomy.

Comparative evaluation of continuous infusion versus programmed intermittent bolus techniques in erector spinae plane block in modified radical mastectomy - A preliminary randomised controlled trial.

Background and Aims: Single-shot erector spinae plane block (ESPB) provides excellent analgesia in mastectomy in the immediate post-operative period but is not sufficient to maintain for prolonged duration. This study compares the efficacy of programmed intermittent bolus (PIB) versus continuous infusion (CI) techniques after ESPB by placing a catheter for mastectomy. Methods: After ethical approval and patient consent, ESPB was performed at the T4 level in 50 patients with an initial bolus of 20 mL 0.375% ropivacaine and a catheter placed 30 min before surgery. In the postoperative period, they were randomised to Group I - intermittent bolus of 20 mL 0.2% ropivacaine every 4 h for 24 h and Group C - continuous infusion of 0.2% ropivacaine at 5 mL/h for 24 h. The primary outcome was the 24-h fentanyl consumption by patient-controlled analgesia device. Data was analysed using Stata 14.0. Results: Group I patients had reduced post-operative fentanyl consumption {mean [standard deviation (SD)]: 166 (139.17) µg vs 332 (247.96) µg, P = 0.002} and lower median NRS scores (1 h: 3 vs 5), (2 h: 3 vs 5), (4 h: 3 vs 5), (6 h: 4 vs 5) with a higher mean (SD) Quality of Recovery-15 score {134.4 (8.53) vs 127 (12.89), P = 0.020} compared to Group C, respectively. The 24-h dermatomal sensory coverage was more comprehensive in Group I compared to Group C. Conclusion: The PIB technique after ESPB provides decreased postoperative opioid consumption, better post-operative analgesia and quality of recovery compared to the CI technique in patients undergoing mastectomy.

Subcutaneous Bolus Infusions of Undiluted Levetiracetam for End-of-Life Patients: Two Cases.

We present two cases, in which end-of-life patients were inadvertently treated with bolus infusions of undiluted subcutaneous levetiracetam. The patients were treated for three and four days respectively. In both cases, the course of treatment was uneventful. Especially, no seizures, nor local irritation was observed. Administration of undiluted subcutaneous levetiracetam as intermittent bolus infusions by hand holds alluring properties for end-of-life patients. Amongst others reducing patient discomfort, increasing freedom of movement, and accessibility to essential seizure prophylaxis by eliminating the need for a syringe driver, thereby helping accommodate many patients wish to die in their own home. However, pharmacokinetics, efficacy, and safety, including the optimum dilution and administration time of the subcutaneous preparation remains to be determined in clinically controlled trials.

Comparative retrospective review of perioperative analgesia using ultrasound-guided programmed intermittent erector spinae plane block for video-assisted thoracoscopic lobectomy.

BACKGROUND: The retrospective cohort study was conducted to estimate the opioid-sparing anesthesia and limited side-effects with ultrasound (US)-guided ESPB using programmed intermittent bolus (PIB) or continuous infusion (CI) and standard opioid-based anesthesia in patients undergoing video-assisted thoracoscopic lobectomy (VATS). METHODS: Patients underwent VATS were stratified into either control group or one of the two ESPB groups in a 1:2:2 ratio depending on whether PIB was implemented or not. The primary endpoint was intra- and post-operative opioids consumption over the first 48 h following surgery. RESULTS: A total of 180 cases were included in the analysis. Cumulative perioperative opioid administration was found to be significantly different between PIB, CI and control group (both p < 0.001), and between PIB and CI group (p = 0.028). More specifically, the mean was 305.30 ± 51.35 mg, 339.68 ± 56.07 mg and 468.91 ± 79.84 mg in PIB, CI and control group. NRS scores at rest across all postoperative times were comparable in two ESPB groups, while significantly lower than control group, however, scores during exercising at postoperative 3, 6, 12 h were significantly lower in PIB group as compared to CI group. A wider anesthetized dermatomes with PIB was observed at 6, 24 and 48 h as opposed to the CI. The mean of levobupivacaine plasma concentration was significantly lower for PIB at postoperative 0.5, 12, 24 and 48 h after initiation than CI. However, local anesthetic toxicity was not observed in any of the two ESPB groups. CONCLUSIONS: When US-guided ESPB using PIB was performed preoperatively, it contributed to the minimization of intra- and post-operative opioid consumption due to better analgesia with a wider anesthetic dermatome opposed to conventional CI, whereas, it was also associated with lower risk of local anesthetic toxicity because of lower plasma concentration of levobupivacaine.

Comparing Continuous and Intermittent Infusion Effects on Serratus Anterior Plane Blocks in Video-Assisted Thoracoscopic Surgery: A Randomized Clinical Trial.

Objective: The programmed intermittent bolus infusion (PIBI) of local anesthetic produces wider sensory blockade and better analgesia than continuous infusion (CI). We designed this trial to compare the effects of these two different infusion methods combined with Serratus Anterior Plane Blocks (cSAPBs) on postoperative pain relief in patients undergoing video-assisted thoracoscopic surgery. Methods: We randomly allocated 66 patients under going elective video-assisted thoracoscopic unilateral lung resection surgery to two groups (PIBI group and CI group, n=33 per group). After the surgical operation, the patients received ultrasound-guided ipsilateral SAPB, we randomized them to receive either automated intermittent boluses or continuous infusion of 0.3% ropivacaine. Tramadol consumption during the 48 hours following surgery was the primary outcome. Secondary outcomes included cumulative tramadol consumption during the first 24-h and the second 24-h periods after surgery, pain scores, patient satisfaction, blocked dermatomes, and adverse events. Results: During 48h, tramadol consumption in the PIBI group was significantly lower than in the CI group (190 mg [125, 305] vs 220 mg [170, 480], p= 0.034). As compared to the CI group, the PIBI group consumed less tramadol during the first 24 hours (145 mg [87.5, 210] vs 190 mg [140, 400], p=0.012). The dermatomes anesthetized to the pinprick and cold test were significantly more abundant in the PIBI group than in the CI group (3 [3,4] vs. 5 [4,5], p<0.001). Both groups had similar VAS scores at rest and when moving (p>0.05). Additionally, the PIBI group showed greater patient satisfaction. Both groups experienced similar adverse events (p>0.05). Conclusion: Compared with CI, PIBI administration regimen (0.3% ropivacaine 5 mL/h) for cSAPBs resulted in lower tramadol consumption, superior analgesia during the initial 12 h after the operation, and higher patient satisfaction. PIBI combined with cSAPBs was a better choice for postoperative analgesia in patients undergoing video-assisted thoracoscopic surgery.

Dural Puncture Epidural with 25-G Spinal Needles versus Conventional Epidural Technique in Conjunction with PIEB for Labor Analgesia: A Randomized Trial.

Purpose: To compare the effect of Dural puncture epidural (DPE) and conventional epidural (EP), in conjunction with programmed intermittent epidural bolus (PIEB) and low-concentration ropivacaine strategy. Methods: After written informed consent was obtained, healthy nulliparous women with singleton pregnancies, vertex presentation at 38-42 weeks' gestation, cervical dilation of 3-5 cm, and a desire for pain relief were randomly assigned to DPE or EP group. Dural matter was puncture with 25G Whitacre needle in DPE group. Analgesia was initiated with 15 mL of 0.1% ropivacaine over 5 minutes and was maintained by PIEB (8 mL of 0.08% ropivacaine with 2 µg/mL fentanyl every 40 min). Primary outcome was the percentage of adequate analgesia, defined as NRPS ≤1, at 30 minutes after the initiation of the epidural bolus. Results: Out of 130 enrolled parturients, 127 were included in final analysis (64 in DPE group, 63 in EP group). No significant difference was found in percentage of adequate analgesia at 30 minutes (risk ratio: 1.09; 95% confidence interval: 0.90-1.31; P = 0.366). At 8, 12, 14, and 16 minutes, percentage of adequate analgesia was higher in DPE group (P = 0.023, 0.027, 0.016 and 0.033, respectively). NPRS scores in DPE group decreased more dramatically within the first 30 min. The incidence of S2 sensory blocks at 20 and 30 min in DPE group was higher (P = 0.010 and 0.006, respectively). There were no differences in patient satisfaction, delivery mode, adverse effects, fetal bradycardia, and Apgar scores at 1 and 5 minutes. Conclusion: The combination of the use of DPE technique with 25G spinal needle and PIEB technique for labor analgesia appears to enhance the quality of labor analgesia by accelerating onset and providing improved sacral blockade, without increasing adverse effects.

Combined Programmed Intermittent Bolus and Patient-Controlled Bolus Is a More Favorable Setting for Epidural Pain Relief Than Continuous Infusion.

Epidural analgesia is a suitable and effective treatment for labor pain. However, the preferable modality setting for delivery remains debatable. This study adopted a programmed intermittent epidural bolus (PIEB) setting in conjunction with a patient-controlled epidural analgesia (PCEA) setting to improve the quality of labor analgesia and reduce the number of medical staff. We conducted a prospective observational analysis of primigravida parturients scheduled for spontaneous labor, which required epidural analgesia for painless labor. A total of 483 healthy primigravida parturients with singleton pregnancies were included in this cohort; 135 nulliparous patients were assigned to the continuous infusion setting (CEI) group and 348 to the PIEB + PCEA group. Compared to the CEI setting, the PIEB + PCEA setting significantly reduced the manual rescue by the clinician, extended the time required for the first manual rescue dose, and acclaimed good maternal satisfaction. The use of the CEI mode increased for poor performance requiring more than two rescues with an odds ratio of 2.635 by a binary logistic regression analysis. Using the PIEB + PCEA setting as the maintenance infusion had a longer duration for the first requested manual rescue, fewer manual rescue boluses, excellent satisfaction, and no significant increase in adverse events compared to the CEI setting.

Intermittent bolus versus continuous feeding in children receiving an enteral formula with food derived ingredients: A national multicentre retrospective study.

BACKGROUND AND AIM: A perceived factor believed to have an impact on feed tolerance relates to the mode in which nutrition is delivered regarding intermittent bolus or continuous feeding. Enteral formulas with food derived ingredients have been developed to help address some of the many feeding issues experienced by children who are tube fed. This study aimed to evaluate the tolerance of different feeding modes in children who are fed with an enteral formula with food derived ingredients. METHODS: Data was collected by paediatric dietitians from dietetic records over a month period on children who had switched to an enteral formula with food derived ingredients. Data was inputted to a Microsoft form to capture the impact of varying modes of feeding (intermittent bolus/continuous/combination) on gastrointestinal and anthropometric outcomes. RESULTS: Forty-three children were recruited between March 2021 to July 2021 across four National Health Service Trusts. Children who were continuously fed saw the greatest reported improvement in retching, abdominal pain and loose stools. Children who were fed intermittent bolus reported the greatest increase in weight (p-value 0.003). Over 90% of dietitians reported nutritional goals were achieved after switching formula; children who were fed continuously reported the highest achievement to meet dietitian's nutritional goals. CONCLUSION: Enteral formulas with food derived ingredients are well tolerated and effective in achieving weight gain and meeting dietetic goals whether delivered continuously or as intermittent bolus feed. The clinical situation will determine the most appropriate and effective feeding mode and should be guided by the dietitian and medical team.

A prospective double-blinded randomized control trial comparing erector spinae plane block to thoracic epidural analgesia for postoperative pain in video-assisted thoracic surgery.

OBJECTIVES: To compare the analgesic efficacies of erector spinae plane (ESP) block and thoracic epidural analgesia (TEA) in video-assisted thoracic surgery (VATS). METHODS: Sixty patients undergoing VATS received patient-controlled TEA with a basal rate of 3 ml/hour (h), a bolus of 3 ml (Group E), or ESP block with programmed intermittent bolus infusions of 15 mL/3 h and a bolus of 5 ml (Group ES) for 2 postoperative days. The primary outcome was to compare pain scores at rest 24 h postoperatively between the 2 groups. Secondary outcomes included NRS score for 48 h, procedural time, dermatomal spread, use of rescue medication, adverse events, and patient satisfaction. RESULTS: Patients with continuous ESP block had a higher NRS score than those with TEA but no statistical difference at a specific time. The dermatomal spread was more extensive in the TEA group than in the ESP block group (p=0.016); cumulative morphine consumption was higher in the ESP block group (p=0.047). The incidence of overall adverse events in the TEA group was higher than in the ESP block group (p=0.045). CONCLUSION: Erector spinae plane block may be inferior to TEA for analgesia following VATS, but it could have tolerable analgesia and a better side effect profile than TEA. Therefore, it could be an alternative to TEA as a component of multimodal analgesia.

Ultrasound-guided, continuous erector spinae plane (ESP) block in minimally invasive thoracic surgery-comparing programmed intermittent bolus (PIB) vs continuous infusion on quality of recovery and postoperative respiratory function: a double-blinded randomised controlled trial.

BACKGROUND: Minimally invasive thoracic surgery (MITS) has been shown to reduce postoperative pain and contribute to better postoperative quality of life as compared to open thoracic surgery (Bendixen et al., Lancet Oncol 17:836-44, 2016). However, it still causes significant post-operative pain. Regional anaesthesia techniques including fascial plane blocks such as the erector spinae plane block (ESP) have been shown to contribute to post-operative pain control after MITS (Finnerty et al., Br J Anaesth 125:802-10, 2020). Case reports relating to ESP catheters have described improved quality of pain relief using programmed intermittent boluses (PIB) instead of continuous infusion (Bendixen et al., Lancet Oncol 17:836-44, 2016). It is suggested that larger, repeated bolus dose may provide superior pain relief, possibly because of improved spread of the local anaesthetic medications (Ilfeld and Gabriel, Reg Anesth Pain Med 44:285-86, 2019). Evidence for improved spread of local anaesthetic may be found in one study which demonstrated that PIB increased the spread of local anaesthetic medication compared to continuous infusions for continuous paravertebral blocks, which are another type of regional anaesthesia technique for the chest wall (Hida et al., Reg Anesth Pain Med 44:326-32, 2019). Similarly, regarding labour epidural analgesia, the weight of evidence is in favour of PIB providing better pain relief compared with continuous infusion (Onuoha, Anesthesiol Clin 35:1-14, 2017). Since fascial plane blocks, such as ESP, rely on the spread of local anaesthetic medication between muscle layers of the chest wall, intermittent boluses may be particularly useful for this group of blocks. However, until recently, pumps capable of providing automated boluses in addition to patient-controlled boluses were not widely available. To best of our knowledge, there are no randomised controlled trials comparing continuous infusion versus intermittent bolus strategies for erector spinae plane block for MITS in terms of patient centred outcomes such as quality of recovery. METHODS: This trial will be a prospective, double-blinded, randomised controlled superiority trial. A total of 60 eligible patients will be randomly assigned to receive an intermittent bolus regime of local anaesthetic vs a continuous infusion of local anaesthetic. The medication will be delivered via an ultrasound-guided erector spinae plane block catheter which will be inserted by an anaesthesiologist while the patient is under general anaesthetic before their MITS surgery begins. The primary outcome being measured is the Quality of Recovery (QoR-15) score between the two groups 24 h after surgery. Secondary outcomes include respiratory testing of maximal inspiratory volume measured with a calibrated incentive spirometer, area under the curve for Verbal Rating Score for pain at rest and on deep inspiration versus time over 48 h, total opioid consumption over 48 h, QoR-15 score at 48 h and time to first mobilisation. DISCUSSION: Despite surgical advancements in thoracic surgery, severe acute post-operative pain following MITS is still prevalent. This study will provide new knowledge and possible recommendations about the efficacy of programmed intermittent bolus regimen of local anaesthetic vs a continuous infusion of local anaesthetic via an ultrasound-guided erector spinae plane catheter for patients undergoing MITS. TRIAL REGISTRATION: This trial was pre-registered on ClinicalTrials.gov Identifier: NCT05181371 . Registered on 6 January 2022. All item from the World Health Organization Trial Registration Data set have been included.

The Effects of Programmed Intermittent Paravertebral Bolus Infusion on Postoperative Analgesia in Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Prospective, Randomized, Controlled Study.

OBJECTIVES: To compare the effects of programmed intermittent bolus infusion (PIBI), continuous thoracic paravertebral infusion (CTPI), and continuous intravenous infusion (CII) on postoperative analgesia in patients undergoing video-assisted thoracoscopic surgery (VATS). DESIGN: Prospective, randomized, controlled. SETTING: The operating room, post-anesthesia care unit, and patient ward of a university hospital. PARTICIPANTS: Ninety patients with American Society of Anesthesiologists (ASA) physical status Ι to II, aged 35-70 years, and scheduled for VATS. INTERVENTIONS: Postoperative analgesia was randomized to PIBI, CTPI, and CII. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the numeric rating scale (NRS) score at rest and during coughing at 1, 4, 24, and 48 hours after surgery. The secondary outcomes included the actual and effective numbers of patient-controlled analgesia (PCA), ropivacaine use, Ramsay sedation scale score, quality of recovery-15 (QoR-15) score, values of hemodynamic parameters at different periods, intraoperative consumption of anesthetic drugs, and postoperative adverse events. Postoperatively, the NRS score was reduced in the PIBI group compared with the CTPI and CII groups at rest and during coughing (p < 0.05). The number of PCAs was significantly lower in the PIBI group compared with the CTPI and CII groups (p < 0.05). The QoR-15 score noticeably increased in the PIBI group compared with the CTPI and CII groups (p = 0.001 and p = 0.000, respectively). CONCLUSIONS: PIBI outperformed CTPI and CII in inducing analgesia for postoperative pain in patients undergoing VATS.

Effects of Different 0.2% Ropivacaine Infusion Regimens for Continuous Interscalene Brachial Plexus Block on Postoperative Analgesia and Respiratory Function After Shoulder Arthroscopic Surgery: A Randomized Clinical Trial.

Objective: Continuous interscalene brachial plexus block (cIBPB) is an effective perioperative analgesic therapy for shoulder arthroscopic surgery (SAS) patients. This trial aimed to compare the effect of different cIBPB infusion methods on postoperative analgesia and respiratory function in patients undergoing SAS. Methods: After SAS, 88 patients were randomly assigned to four groups. Through interscalene catheter, all the patients received an initial dose of 10 mL 0.2% ropivacaine. The CI group received 0.2% ropivacaine 4 mL/h, and the PIBI1, PIBI2, and PIBI3 groups received intermittent 0.2% ropivacaine boluses at 4 mL/h, 8 mL/2 h, and 12 mL/3 h, respectively. The patients could also use a patient-controlled analgesia (PCA) pump to self-inject a tramadol bolus each time he/she felt pain. The primary outcome was the cumulative tramadol consumption over the 48 h after surgery. Secondary outcome measures included PCA frequency, pain (visual analogue scale, VAS) score, patient satisfaction, diaphragmatic excursion, pulmonary function, and adverse events. Results: The cumulative tramadol consumption and PCA frequency over the 48 h after surgery in groups PIBI2 and PIBI3 were lower than in both the CI and PIBI1 groups (p<0.001). The VAS scores (at rest and on movement) in groups PIBI2 and PIBI3 were lower than those in the CI and PIBI1 groups at 8 and 12 h after surgery (all p<0.001). Patient satisfaction scores were significantly higher in the PIBI2 group than in the other three groups (all p<0.001). Diaphragmatic excursion was significantly decreased in the PIBI3 group compared to the other three groups (p<0.05). The incidence of adverse events over the 48 h after surgery was significantly higher in the PIBI3 group compared to the other three groups (p<0.001). Conclusion: Programmed intermittent bolus infusion with 0.2% ropivacaine 8 mL/2 h for cIBPB can achieve lower tramadol consumption, along with better analgesia after surgery, lower reduction in diaphragmatic excursion, lower incidence of adverse events, and higher patient satisfaction.

Intermittent boluses of balanced salt solution for post-operative intravenous hydration following elective major abdominal and thoracic surgery in children.

PURPOSE: Maintenance fluids following major operations in children are typically administered with a continuous rate. We hypothesized that administering fluids as intermittent boluses is more physiologic and could limit post-operative fluid volume, thereby avoiding harmful effects of excess fluid. METHODS: We retrospectively reviewed children aged 1-21 admitted after an elective major abdominal or thoracic operation from 2015 to 2021. We excluded non-elective operations and patients receiving peri-operative enteral or parenteral nutrition. We analyzed total fluid volume at 0-24, 24-48, 48-72, and 72-96 h, time to regular diet and discharge, and end-organ complications. RESULTS: We identified 363 patients, of which 108 received intermittent boluses and 255 continuous fluids. Bolus group patients received significantly less fluid up to 72 h post-operatively with average rates of 0.49 mL/kg/h vs 0.86 mL/kg/h at 0-24 h (p << 0.01), 0.57 mL/kg/h vs 1.46 mL/kg/h at 24-48 h (p << 0.01), and 0.50 vs 0.92 mL/kg/h at 48-72 h (p << 0.01). Additionally, the bolus group maintained adequate urine output, tolerated a regular diet sooner (2.08 days vs 2.51 days; p = 0.0023) and averaged a shorter hospital stay (3.12 vs 4.14 days; p = 0.004). There was no difference in adverse effects between the two groups. CONCLUSION: Utilizing intermittent boluses reduces the volume of maintenance fluids administered and may lead to a faster time to regular diet and discharge. LEVEL OF EVIDENCE: IV. TYPE OF STUDY: Retrospective review.

Programmed intermittent epidural bolus for labour analgesia: a randomized controlled trial comparing bolus delivery speeds of 125 mL·hr-1 versus 250 mL·hr-1.

PURPOSE: Programmed intermittent epidural bolus (PIEB) provides better analgesia for labour pain than continuous epidural infusion does. Nevertheless, commonly used PIEB regimens are associated with high sensory block. We hypothesized that a PIEB technique with slower bolus delivery speed would produce lower sensory levels. METHODS: We recruited term nulliparous women with singleton pregnancies during the first stage of labour. All participants had an American Society of Anesthesiologists Physical Status score of II-III, had epidural catheters placed at L3/4, and had epidural analgesia maintained with PIEB 10 mL every 40 min using 0.0625% bupivacaine with fentanyl 2 µg·mL-1. Women were randomized to receive PIEB delivered at 250 mL·hr-1 (G250) or 125 mL·hr-1 (G125). The study was completed six hours after the loading dose or at full cervical dilatation, whichever occurred first. The primary outcome was the presence of sensory block to ice ≥ T6 in at least one assessment during the study period (maximum six hours). RESULTS: We analyzed data from 90 women. The proportion of women presenting sensory block ≥ T6 at any time was not different between G125 and G250 groups (60.0% vs 64.4%; difference, -4.4%; 95% confidence interval [CI], -24.5 to 15.6; P = 0.66). The median [interquartile range] highest sensory block level was also not different between G125 and G250 groups (T6 [T7-T5] vs T5 [T7-T5], P = 0.39). Women in the G125 group had a lower incidence of hypotension than women in the G250 group did (11.1% vs 33.3%; difference, -22.2%; 95% CI, -38.8 to -5.67; P = 0.01). Quality of analgesia and patient satisfaction were not different between groups. CONCLUSION: The maintenance of epidural analgesia with a PIEB delivery speed of 125 mL·hr-1 did not produce lower sensory block levels when compared with 250 mL·hr-1. The slower injection speed regimen was associated with lower incidence of hypotension, but this secondary finding warrants confirmation in a future trial. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT03236298); registered 1 August 2017.

RéSUMé: OBJECTIF: L'administration programmée intermittente de bolus périduraux (PIEB, pour programmed intermittent epidural bolus) fournit une meilleure analgésie pour la douleur du travail que l'analgésie péridurale par perfusion continue. Néanmoins, les régimes de PIEB couramment utilisés sont associés à un bloc sensoriel élevé. Nous avons émis l'hypothèse qu'une technique de PIEB avec une vitesse d'administration plus lente du bolus produirait des niveaux sensoriels inférieurs. MéTHODE: Nous avons recruté des femmes nullipares à terme ayant des grossesses uniques au cours de la première étape du travail obstétrical. Toutes les participantes avaient un score de statut physique II-III de l'American Society of Anesthesiologists, des cathéters périduraux placés au niveau L3/4 et une analgésie péridurale maintenue avec des PIEB de 10 mL de bupivacaïne 0,0625 % et de 2 µg·mL-1 de fentanyl, administrés toutes les 40 minutes. Les femmes ont été randomisées à recevoir des PIEB administrés à une vitesse de 250 mL·h-1 (G250) ou 125 mL·h-1 (G125). L'étude se terminait six heures après la dose de charge ou lors de la dilatation cervicale complète, selon la première éventualité. Le critère d'évaluation principal était la présence d'un bloc sensoriel à la glace ≥ T6 lors d'au moins une évaluation au cours de la période à l'étude (pour un maximum de six heures). RéSULTATS: Nous avons analysé les données de 90 femmes. La proportion de femmes présentant un bloc sensoriel ≥ T6 à tout moment n'était pas différente entre les groupes G125 et G250 (60,0 % vs 64,4 %; différence, -4,4 %; intervalle de confiance [IC] à 95 %, -24,5 à 15,6; P = 0,66). Le niveau médian [écart interquartile] le plus élevé de bloc sensoriel n'était pas non plus différent entre les groupes G125 et G250 (T6 [T7-T5] vs T5 [T7-T5], P = 0,39). Les femmes du groupe G125 avaient une incidence d'hypotension plus faible que les femmes du groupe G250 (11,1 % vs 33,3 %; différence, -22,2 %; IC 95 %, -38,8 à -5,67; P = 0,01). La qualité de l'analgésie et la satisfaction des patientes n'étaient pas différentes d'un groupe à l'autre. CONCLUSION: Le maintien de l'analgésie péridurale avec une vitesse d'administration des PIEB de 125 mL·h-1 n'a pas entraîné de taux de blocs sensoriels inférieurs par rapport à une vitesse de 250 mL·h-1. Le régime de vitesse d'injection plus lente a été associé à une incidence plus faible d'hypotension, mais cette constatation secondaire mérite d'être confirmée dans une étude future. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03236298); enregistrée le 1er août 2017.

Efficacy of programmed intermittent bolus epidural analgesia in thoracic surgery: a randomized controlled trial.

BACKGROUND: Continuous epidural infusion (CEI) has some disadvantages, such as increased local anesthetic consumption and limited area of anesthetic distribution. Programmed intermittent bolus (PIB) is a technique of epidural anesthesia in which boluses of local anesthetic are automatically injected into the epidural space. The usefulness of PIB in thoracic surgery remains unclear. In this study, we aimed to compare the efficacies of PIB epidural analgesia and CEI in patients undergoing thoracic surgery. METHODS: This randomized prospective study was approved by the Institutional Review Board. The study included 42 patients, who were divided into CEI (n = 21) and PIB groups (n = 21). In the CEI group, patients received continuous infusion of the local anesthetic at a rate of 5.1 mL/90 min. In the PIB group, a pump delivered the local anesthetic at a dose of 5.1 mL every 90 min. The primary endpoints were the frequency of patient-controlled analgesia (PCA) and the total dose of local anesthetic until 36 h following surgery. Student's t-test, the chi-square test, and the Mann-Whitney U test were used for statistical analyses. RESULTS: The mean number of PCA administrations and total amount of local anesthetic were not significantly different between the two groups up to 24 h following surgery. However, the mean number of PCA administrations and total amount of local anesthetic at 24-36 h after surgery were significantly lower in the PIB group than in the CEI group (median [lower-upper quartiles]: 0 [0-2.5] vs. 2 [0.5-5], P = 0.018 and 41 [41-48.5] vs. 47 [43-56], P = 0.035, respectively). Hypotension was significantly more frequent in the PIB group than in the CEI group at 0-12 h and 12-24 h (3.3% vs. 0.5%, P = 0.018 and 7.9% vs. 0%, P = 0.017, respectively). CONCLUSION: PIB can reduce local anesthetic consumption in thoracic surgery. However, it might result in adverse events, such as hypotension. TRIAL REGISTRATION: This randomized prospective study was approved by the Institutional Review Board (IRB No. 15-9-06) of the Fukuoka University Hospital, Fukuoka, Japan, and was registered in the clinical trials database UMIN ( ID 000019904 ) on 24 November 2015. Written informed consent was obtained from all patients.

Comparison between total intravenous anesthesia with propofol and intermittent bolus of tiletamine-zolazepam in capuchin monkey (Sapajus apella) / Comparação entre anestesia total intravenosa com propofol e bolus intermitente de tiletamina-zolazepam em macaco-prego (Sapajus apella)

Dissociative anesthesia results in stressful and long recovery periods in monkeys and use of injectable anesthetics in medical research has to be refined. Propofol has promoted more pleasure wake up from anesthesia. The objectives of this study were to investigate the use of intravenous anesthetic propofol, establishing the required infusion rate to maintain surgical anesthetic level and comparing it to tiletamine-zolazepam anesthesia in Sapajus apella. Eight healthy capuchin monkeys, premedicated with midazolam and meperidine, were anesthetized with propofol (PRO) or tiletamine-zolazepam (TZ) during 60 minutes. Propofol was infused continually and rate was titrated to effect and tiletamine-zolazepam was given at 5mg/kg IV bolus initially and repeated at 2.5mg/kg IV bolus as required. Cardiopulmonary parameters, arterial blood gases, cortisol, lactate and quality and times to recovery were determined. Recovery quality was superior in PRO. Ventral recumbency (PRO = 43.0±21.4 vs TZ = 219.3±139.7 min) and normal ambulation (PRO = 93±27.1 vs TZ = 493.7±47.8 min) were faster in PRO (p<0.05). Cardiopulmonary effects did not have marked differences between groups. Median for induction doses of propofol was 5.9mg/kg, varying from 4.7 to 6.7mg/kg, Mean infusion rate was 0.37±0.11mg/kg/min, varying during the one-hour period. In TZ, two animals required three and five extra doses. Compared to tiletamine-zolazepam, minor post-anesthetic adverse events should be expected with propofol anesthesia due to the faster and superior anesthetic recovery. (AU)

A anestesia dissociativa em primatas resulta em recuperação anestésica lenta e estressante, e, portanto, o uso de anestesia injetável em pesquisas médicas precisa ser refinado. Por outro lado, o propofol promove recuperação mais suave. Os objetivos desse estudo foram investigar o uso do anestésico intravenoso propofol, estabelecer a taxa de infusão contínua necessária para manter anestesia cirúrgica, e comparar tal técnica com a dissociativa tiletamina-zolazepam em Sapajus apella. Oito macacos-prego saudáveis foram pré-medicados com midazolam e meperidina, e posteriormente anestesiados com propofol (PRO) ou tiletamina-zolazepam (TZ) durante 60 minutos. O propofol foi administrado em infusão contínua, e a taxa foi titulada ao efeito, já a tiletamina-zolazepam foi administrada em 5mg/kg IV como bolus inicial, e repiques de 2,5mg/kg IV conforme necessário. Os parâmetros cardiopulmonares, hemogasometria arterial, cortisol, e lactato, além da qualidade e duração da recuperação anestésica foram determinados. A qualidade da recuperação anestésica foi superior em PRO. O tempo para atingir decúbito ventral (PRO = 43,0±21,4 vs TZ = 219,3±139,7 min) e ambulação normal (PRO = 93±27,1 vs TZ = 493,7±47,8 min) foram mais rápidos em PRO (p<0,05). As variáveis cardiopulmonares não diferiram entre os grupos. A mediana para dose de indução com propofol foi de 5,9mg/kg, variando de 4,7 a 6,7mg/kg. A taxa de infusão contínua média de propofol foi de 0,37±0,11mg/kg/min, variando ao longo dos 60 minutos. Em TZ, dois animais necessitaram de três e cinco repiques. Comparado à tiletamina-zolazepam, menos efeitos adversos pós-anestésicos devem ser esperados com o propofol, devido à recuperação mais suave e rápida.(AU)

Effects of programmed intermittent thoracic paravertebral bolus of levobupivacaine on the spread of sensory block: a randomized, controlled, double-blind study.

BACKGROUND AND OBJECTIVES: This randomized, controlled, double-blind trial compared the effectiveness of levobupivacaine delivery of a programmed intermittent paravertebral bolus with a continuous paravertebral infusion. METHODS: Thirty-two consecutively enrolled patients who underwent unilateral video-assisted thoracic surgery were randomized to receive either a programmed intermittent paravertebral bolus of 10 mL of 0.2% levobupivacaine every 2 hours (Bolus group, n=16) or a continuous paravertebral infusion of 0.2% levobupivacaine at 5 mL/hour (Infusion group, n=16) after the operation. Postoperatively, after injection of 20 mL of 0.25% levobupivacaine through the paravertebral catheter, a mechanical infusion pump was set depending on the assigned group. The primary efficacy outcome was the number of anesthetized dermatomes 24 hours after the initial bolus of levobupivacaine. The secondary efficacy outcomes included the number of anesthetized dermatomes at other time points, pain at rest and coughing, additional analgesic use and patient acceptance of the analgesic technique. Arterial levobupivacaine concentration was measured to ensure safety. P<0.05 was considered statistically significant. RESULTS: The mean (95% CI) number of anesthetized dermatomes 24 hours after the initial bolus of levobupivacaine was significantly larger among subjects receiving programmed intermittent bolus (n=16) compared with those receiving continuous infusion (n=16; 6.8 (5.7-7.9) vs 3.1 (2.0-4.2); p<0.001). The arterial levobupivacaine concentration did not reach a toxic level. CONCLUSIONS: The programmed intermittent paravertebral bolus of levobupivacaine provided a wider dermatomal spread of sensory block than continuous paravertebral infusion with an identical hourly dose of levobupivacaine. TRIAL REGISTRATION NUMBER: UMIN000022532.

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

OBJECTIVE: Adequate 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 fentanyl for analgesia and sedation in neonates. METHODS: In this open-label randomised controlled trial, neonates requiring 24-48 hours of mechanical ventilation and fentanyl administration were recruited. In CI regimen, 1 mcg/kg loading dose was followed by 1 mcg/kg/hour infusion. In IB regimen, 1mcg/kg/dose was administered every 4 hours.Maximum six blood samples were collected in 48 hours from each baby at prespecified time points for estimating serum fentanyl concentration. Secondary outcomes were pain scores (Neonatal Infant Pain Scale and Neonatal Pain, Agitation and Sedation Scale for acute and ongoing pain, respectively) and incidence of adverse effects of fentanyl. RESULTS: 100 neonates were recruited, 53 in CI and 47 in IB group. In CI regimen, median (IQR) serum fentanyl concentration was 0.42 (0.35, 0.46) to 0.61 (0.47, 0.89) ng/mL throughout the infusion period. In IB regimen, median (IQR) peak concentration ranged from 2.21 (1.82, 3.55) to 3.61 (2.91, 4.51) ng/mL and trough concentration 0.41 (0.33, 0.48) to 0.97 (0.56, 1.25) ng/mL for various doses.Median (IQR) peak concentration (Cmax, 3.06 (1.09, 4.50) vs 0.78 (0.49, 1.73) ng/mL; p<0.001) was significantly higher and area under concentration-time curve (AUC0-24, 19.6 (10.4, 33.5) vs 13.2 (10.8, 22.6) µg·hour/L; p=0.12) was higher (though not statistically significant) in IB than CI regimen. Pain scores and adverse effects were comparable between the two regimens. CONCLUSION: CI regimen of fentanyl produces steady serum concentrations, whereas IB regimen produces wide fluctuations in serum concentration with high-peak concentrations. A serum fentanyl concentration of 0.4-0.6 ng/mL produces adequate analgesia and sedation in neonates. TRIAL REGISTRATION NUMBER: CTRI/2014/11/005190.

Neuraxial techniques of labour analgesia.

In recent years, many neuraxial techniques have been introduced to initiate and maintain labour analgesia, with low-dose mixtures of local anaesthetics and opioids, which have improved the quality of analgesia and made it safer for both mother and neonate. An independent search of the databases of PubMed, Medline, and Cochrane controlled trial data was conducted by two researchers, and randomized controlled trials that compared different methods of neuraxial analgesia and the different techniques of maintaining labor analgesia were retrieved and analyzed. The advantages, disadvantages, and indications of each technique along with the doses of intrathecal and epidural drugs are discussed. The myths and controversies involving neuraxial labor analgesia and the current consensus on their effect on the maternal and foetal outcomes are also outlined.