Postoperative pain treatment with erector spinae plane block and pectoralis nerve blocks in patients undergoing mitral/tricuspid valve repair - a randomized controlled trial.

BACKGROUND: Effective postoperative pain control remains a challenge for patients undergoing cardiac surgery. Novel regional blocks may improve pain management for such patients and can shorten their length of stay in the hospital. To compare postoperative pain intensity in patients undergoing cardiac surgery with either erector spinae plane (ESP) block or combined ESP and pectoralis nerve (PECS) blocks. METHODS: This was a prospective, randomized, controlled, double-blinded study done in a tertiary hospital. Thirty patients undergoing mitral/tricuspid valve repair via mini-thoracotomy were included. Patients were randomly allocated to one of two groups: ESP or PECS + ESP group (1:1 randomization). Patients in both groups received a single-shot, ultrasound-guided ESP block. Participants in PECS + ESP group received additional PECS blocks. Each patient had to be extubated within 2 h from the end of the surgery. Pain was treated via a patient-controlled analgesia (PCA) pump. The primary outcome was the total oxycodone consumption via PCA during the first postoperative day. The secondary outcomes included pain intensity measured on the visual analog scale (VAS), patient satisfaction, Prince Henry Hospital Pain Score (PHHPS), and spirometry. RESULTS: Patients in the PECS + ESP group used significantly less oxycodone than those in the ESP group: median 12 [interquartile range (IQR): 6-16] mg vs. 20 [IQR: 18-29] mg (p = 0.0004). Moreover, pain intensity was significantly lower in the PECS + ESP group at each of the five measurements during the first postoperative day. Patients in the PECS + ESP group were more satisfied with pain management. No difference was noticed between both groups in PHHPS and spirometry. CONCLUSIONS: The addition of PECS blocks to ESP reduced consumption of oxycodone via PCA, reduced pain intensity on the VAS, and increased patient satisfaction with pain management in patients undergoing mitral/tricuspid valve repair via mini-thoracotomy. TRIAL REGISTRATION: The study was registered on the 19th July 2018 (first posted) on the ClinicalTrials.gov identifier: NCT03592485.

Fentanyl with ropivacaine infusion for postoperative pain relief in infants and children. Kinetics of epidural fentanyl.

OBJECTIVES: The aim of the study was to evaluate pharmacokinetics of fentanyl administered as continuous epidural infusion with 0.2% ropivacaine for postoperative pain relief in infants and toddlers, and older children undergoing major abdominal and urological procedures. METHODS: Thirteen infants and toddlers (median age 14 [range 3-36] months, 11 [5-17] kg, Group I) and 11 children (68 [45-131] months, 21 [16-52] kg, Group II) participated in the study. Epidural catheter was placed under general anesthesia in the L1-L2, L2-L3, or L3-L4 epidural space and threaded up to 4 cm into the epidural space. Bolus dose of 0.2% ropivacaine, 0.5 ml·kg(-1) and fentanyl, 2 µg·kg(-1) was given, then followed by continuous infusion of 0.2% ropivacaine, 0.15 ml·kg(-1) ·h(-1) with fentanyl 1.12 µg·kg(-1) ·h(-1) . In the postoperative period, fentanyl dose was reduced to 0.375 µg·kg(-1) ·h(-1) . RESULTS: With this dosing regimen, fentanyl concentration in plasma was within the range of analgesic concentrations, and did not exceed 1.0 ng·ml(-1) . After discontinuation of epidural infusion, pharmacokinetics of fentanyl was complicated by a slight increase in plasma concentration during the elimination phase. Both elimination half-life of fentanyl (t1/2, MRT ) and mean residence time (MRT) were much longer than those observed after single IV bolus dose, and longer in Group I than in Group II (t1/2 MRT 15.9 [3.6-31.5] h vs 8.0 [7.1-13.3] h, P < 0.05, MRTstop-last 22.9 [5.1-45.5] h vs 11.5 [10.2-19.1] h, P < 0.05). Therefore, monitoring of vital signs seems warranted for several hours after the termination of the epidural infusion because risk of respiratory depression may persist, especially in the younger age group.

WHY IS NEONATAL ANAESTHESIA SUCH A CHALLENGE?

Approximately 1.5 million neonates receive general anaesthesia each year for surgical procedures. Providing anaesthesia to neonates is not easy. Surgical procedures are often difficult and extensive, and the physiology of neonates makes respiratory and cardiovascular problems more frequent and life-threatening. The paper covers the changing concepts in neonatal anaesthesia, including recent studies that indicate that anaesthetic exposure could cause neuronal apoptosis in the developing brain. This could potentially influence the long-term developmental outcome, especially in infants requiring multiple surgical procedures. Respiratory and cardiovascular critical events, age-related differences of the pharmacokinetics of the drugs used for anaesthesia, as well as technical problems are also covered.

THE VALUE OF THE OXYGENATION INDEX IN THE PREDICTION OF POSTNATAL OUTCOME IN NEONATES WITH CONGENITAL DIAPHRAGMATIC HERNIA. PRELIMINARY REPORT.

UNLABELLED: The predicitive values of fetal ultrasonography and magnetic resonance imaging are well established as antenatal outcome predictors in neonates with congenital diaphragmatic hernia (CHD). Postnatal outcome predictors remain elusive. THE AIM: To evaluate the value of the oxygenation index (OI) as a predictor of postnatal survival. MATERIAL AND METHODS: 58 newborns with congenital diaphragmatic hernia, treated in the same centre (a university hospital) between February 2006 and March 2014 were involved in the retrospective study. Standardized preoperative stabilization involved: sedation without muscle paralysis, high frequency oscillation ventilation (HFOV) and inhaled nitric oxide (iNO, used as required). Oxygenation index OI = FiO2 x 100 x M AP/PaO2, where FiO2 is the fraction of inspired oxygen, MAP is the mean airway pressure, and PaO2 is the partial pressure of oxygen in arterial blood, calculated at the end of the first day of standardized preoperative stabilization, and evaluated as a predictor of survival. RESULTS: The overall survival rate on the hospital discharge was 74.1%. As far as the oxygenation index (OI) at the end of the first day of the preoperative stabilisation is concerned, in 40/43 survivors it was below or equal to 12, in one infant it equalled 12.7, and in two remaining survivors OI was much higher (18 and 56, respectively). The prognostic value of the oxygenation index was high, with the area under the curve (AUC) 0.943, sensitivity 0.930, and specificity 0.876. CONCLUSIONS: The oxygenation index (OI) calculated at the end of the first day of standardized preoperative stabilization with high frequency oscillation ventilation (HFOV) and nitric oxide (iNO) is a simple and sensitive predictor of the survival of neonates with a congenital diaphragmatic hernia. It may be a valuable tool to select high-risk neonates who might require more invasive therapeutic modalities, i.e. extracorporeal membrane oxygenation (ECMO).

Pharmacokinetics of sufentanil administered with 0.2% ropivacaine as a continuous epidural infusion for postoperative pain relief in infants.

BACKGROUND AND OBJECTIVES: Our objective was to assess plasma sufentanil concentrations and postinfusion pharmacokinetics in infants receiving 0.2% ropivacaine with sufentanil as a continuous epidural infusion for postoperative pain relief. METHODS: With consent of local ethics committee and informed parental consent, 20 infants 3-36 months old (m.o.) (median 9.3 m.o., 9.0 [3.5-15] kg, ASA PS I/II) were enrolled. Epidural catheter was placed under general anesthesia in L3-L4, L4-L5, or L2-L3 interspace and threaded not farther than 4 cm into epidural space. After initial bolus of 0.2% ropivacaine, 0.5 ml·kg(-1) and sufentanil 200 ng·kg(-1) , continuous infusion of 0.2% ropivacaine, 0.3 mg·kg(-1) ·h(-1) with sufentanil 112 ng·kg(-1) ·h(-1) was started. For the postoperative period, sufentanil dose was reduced to 37 ng·kg(-1) ·h(-1) . Blood samples were drawn at the end of surgery, 24 h later, by the end of 2nd day of infusion and after 3, 6, and 18 h from the end of infusion. Sufentanil was measured using liquid-liquid extraction (LLE) procedure and HPLC-MS/MS method with LOQ = 5 pg·ml(-1) . RESULTS AND CONCLUSIONS: Elimination of sufentanil following epidural administration was very slow, with MRT = 28.25 [18.36-44.75] h and t1/2 MRT  = 19.57 [12.72-31.01] h. In infants, during a long-term infusion of sufentanil with ropivacaine, the opioid concentration in plasma increases during the postoperative infusion itself, then increases even further after discontinuation of the infusion, in some cases reaching the values consistent with a potential risk of respiratory depression. Meticulous monitoring of the infants' vital signs is therefore mandatory not only during the infusion, but also for several hours after its discontinuation.

Early removal of chest drains in patients following off-pump coronary artery bypass graft (OPCAB) is not inferior to standard care - study in the Enhanced Recovery After Surgery (ERAS) group.

INTRODUCTION: Only a few studies have concerned the timing of chest drains' removal in cardiac surgery patients following the coronary artery bypass graft (CABG). None of them pertained to the off-pump CABG (OPCAB) procedure. AIM: To compare thoracic drainage time in OPCAB patients before the implementation of the institutional Enhanced Recovery After Surgery (ERAS) protocol and after that. MATERIAL AND METHODS: It was a single-center observational study concerning patients following OPCAB. Two groups of patients were analyzed: after implementing the ERAS protocol, the ERAS group, and before this period, the standard care group (STAND group). The primary outcome of this study was to compare postoperative drainage time in the ERAS and STAND groups. The other outcomes included comparing transfused blood products, postoperative complications, surgical technique, postoperative ventilation and the intensive care unit stay time. RESULTS: Sixty patients in the ERAS and 112 in the STAND group were analyzed. The postoperative drainage time was shorter in the ERAS than in the STAND group: 20 (17-22) vs. 30 (27-35) h, p < 0.001. The number of transfused blood products was similar in both groups. No difference was noted between groups according to surgery and anesthesia time. However, patients in the ERAS group were ventilated for a significantly shorter time after the surgery and spent less time in the ICU than the STAND group. The number of postoperative complications in the ERAS and STAND group was 14 and 27, p = 1. CONCLUSIONS: The early removal of chest drains after OPCAB does not increase the risk of postoperative complications and demand for blood products. However, its impact on patients' morbidity needs further studies.

Implementation of Enhanced Recovery After Surgery (ERAS) protocol in off-pump coronary artery bypass graft surgery. A prospective cohort feasibility study.

BACKGROUND: Coronary artery bypass graft (CABG) is the most commonly performed cardiac surgery procedure. Although some complications related to the cardiopulmonary bypass circuit are avoided during off-pump CABG (OP-CABG) procedures, prolonged mechanical ventilation and severe postoperative pain are still important issues. METHODS: This prospective cohort study aimed to assess the impact of the institutional Enhanced Recovery After Surgery (ERAS) protocol in patients undergoing OP-CABG. This protocol contained several modifications to the perioperative period, among which bilateral erector spinae plane block, remifentanil infusion, and patient-controlled analgesia (PCA) with oxycodone were the most important factors (ERAS group). The ERAS group was compared with the retrospective cohort (same surgeon) before the ERAS protocol was implemented (standard care group). The outcomes measured included the postoperative mechanical ventilation time, ICU and hospital stay, postoperative drainage time, postoperative troponin T level, pain severity evaluated via a numerical rating scale, and the total consumption of opioids in both groups of patients. RESULTS: Overall, 57 patients were analyzed - 29 in the ERAS group and 28 in the standard care group. The time of mechanical ventilation, thoracic drainage, and ICU and hospital stay was shorter in the ERAS group than in the standard care group. The pain was less intense in the ERAS patients, and the postoperative opioid demand was reduced. Moreover, the increase of the postoperative troponin T concentration was lower in the ERAS group. CONCLUSIONS: Our study showed that ERAS protocol implementation could improve patient outcomes after OP-CABG surgery.

Remifentanil preconditioning protects against hypoxia-induced senescence and necroptosis in human cardiac myocytes in vitro.

Remifentanil and other opioids are suggested to be protective against ischemia-reperfusion injury in animal models and coronary artery bypass surgery patients, however the molecular basis of such protection is far from being understood. In the present study, we have used a model of human cardiomyocytes treated with the hypoxia-mimetic agent cobalt chloride to investigate remifentanil preconditioning-based adaptive responses and underlying mechanisms. Hypoxic conditions promoted oxidative and nitrosative stress, p21-mediated cellular senescence and the activation of necroptotic pathway that was accompanied by a 2.2-, 9.6- and 8.2-fold increase in phosphorylation status of mixed lineage kinase domain-like pseudokinase (MLKL) and release of pro-inflammatory cytokine IL-8 and cardiac troponin I, a marker of myocardial damage, respectively. Remifentanil preconditioning was able to lower hypoxia-mediated protein carbonylation and limit MLKL-based signaling and pro-inflammatory response to almost normoxic control levels, and decrease hypoxia-induced pro-senescent activity of about 21% compared to control hypoxic conditions. In summary, we have shown for the first time that remifentanil can protect human cardiomyocytes against hypoxia-induced cellular senescence and necroptosis that may have importance with respect to the use of remifentanil to diminish myocardial ischemia and reperfusion injury in patients undergoing cardiac surgery.

Erector spinae-plane block as an analgesic alternative in patients undergoing mitral and/or tricuspid valve repair through a right mini-thoracotomy - an observational cohort study.

INTRODUCTION: One of the main challenges in cardiac surgery is effective postoperative analgesia. Erector spinae-plane block (ESP block) is a novel regional technique, introduced by Forero in 2016 for neuropathic chest pain, then used successfully for mastectomy. AIM: To establish the efficacy of the ESP block in patients undergoing mitral and/or tricuspid valve repair through a right mini-thoracotomy. MATERIAL AND METHODS: It is a prospective observational cohort study performed in a tertiary health center. In the treatment group, a single-shot ESP block was performed before anesthetic induction. General anesthesia was induced with etomidate, remifentanil, and rocuronium, and continued with sevoflurane and remifentanil. Remifentanil infusion was continued for 2 h post-operatively, then stopped, and the patient's trachea was extubated. Patient-controlled analgesia was started with oxycodone immediately. Total oxycodone consumption and pain severity on the visual analog scale during the first 24 h were analyzed. In the control group, no regional block was performed. Instead of remifentanil, fentanyl was used. Patients were extubated on the second day. Pain was treated with morphine, administered according to nurses' discretion. Pain intensity was evaluated on the numerical rating scale. RESULTS: Nineteen patients were evaluated in the ESP and 25 in the control group. Mechanical ventilation time was shorter in the ESP group (0.6 (0.4-1.1) h) than in the control one (10 (8-17) h, p = 0.00001). Moreover, patients in the ESP group spent fewer days in the intensive care unit (1 (1-1) vs. (2 (2-2), p = 0.0001). CONCLUSIONS: The ESP block seems to be safe and efficient for pain control in patients undergoing right mini-thoracotomy for mitral and/or tricuspid valve repair.

Remifentanil and sevoflurane based anesthesia combined with bilateral erector spinae plane block in patients undergoing off-pump coronary artery bypass graft surgery.

INTRODUCTION: Working on the institutional Enhanced Recovery After Surgery (ERAS Cardio) protocol for off-pump coronary artery bypass graft surgery (OP-CABG) we have noticed that patients treated according to the modified anesthesia protocol had not only significantly shorter time of respiratory support and intensive care unit stay but also lower postoperative troponin T concentration than patients who had standard fentanyl/sevoflurane-based anesthesia. AIM: To compare the perioperative course of patients undergoing OP-CABG surgery and receiving standard fentanyl/sevoflurane anesthesia and those anesthetized according to the institutional ERAS Cardio protocol with remifentanil, sevoflurane, and bilateral extensor spinae plane (ESP) block. MATERIAL AND METHODS: Design: a prospective, open-label, observational study performed in a tertiary health center. Participants: 30 consecutive patients undergoing off-pump coronary bypass graft surgery. Interventions: 15 patients had standard anesthesia with etomidate, fentanyl, and rocuronium for induction and fentanyl/sevoflurane for maintenance (standard group); 15 others had bilateral single shot ESP block, then etomidate, remifentanil and rocuronium for induction, and remifentanil/sevoflurane for maintenance of anesthesia. RESULTS: Median time to extubation was 7.6 (5.5-12.5) h and 1.7 (1-3.25) h in "standard care" and ERAS groups, respectively (p = 0.00002). Length of stay in the intensive care unit was also shorter for patients in the ERAS group 20.5 (18-24) vs. 48 (42-48) h (p = 0.00001). Troponin concentration increased to a lesser extent in patients from the ERAS group: an increase of 151.8 (71.9-174.3) ng/ml vs. 253.8 (126.6-373.1) ng/ml, p = 0.008. CONCLUSIONS: Remifentanil/sevoflurane anesthesia combined with bilateral ESP block shortens mechanical ventilation time and ICU stay, and decreases postoperative troponin-T concentration in patients undergoing off-pump coronary bypass graft surgery.

Flip-Flop Phenomenon in Epidural Sufentanil Pharmacokinetics: A Population Study in Children and Infants.

The aims of this study were to develop a population pharmacokinetic model of sufentanil coadministered with 0.2% ropivacaine as an epidural infusion in infants and describe the sufentanil absorption profile from epidural space. Data from 2 previously published studies were merged for analysis-20 infants aged 3-36 months receiving sufentanil as an epidural infusion and 41 children 0-17 years old receiving sufentanil as a long-term intravenous infusion. A population nonlinear mixed-effects model was built in NONMEM. Sufentanil pharmacokinetics were described by a 2-compartment model with first-order absorption. The effect of body size on all volume and clearance parameters was included in the model according to allometric scaling with theoretical exponents. The maturation process of metabolic clearance was described by the Hill model. During the model-building process the population was divided into 2 fractions with different typical values of metabolic clearance (CL1 and CL2). The typical values of systemic clearance scaled to a 70-kg patient for the 2 subpopulations were CL1 = 52.6 L/h and CL2 = 158 L/h. The parameters of the Hill function were 54.9 weeks for the postmenstrual age of 50% clearance maturation and 0.802 for the Hill coefficient. The typical values of distribution clearance and volumes of the central and peripheral compartments for a patient with a weight of 70 kg were Q = 40.5 L/h, VC = 7.63 L, and VT = 473 L, respectively. The value of the absorption rate constant from the epidural space was 0.0459/h, which suggests flip-flop pharmacokinetics of sufentanil after epidural administration.

[Acute normovolaemic haemodilution in children]. / Sródoperacyjna normowolemiczna hemodylucja u dzieci.

Acute normovolemic haemodilution was performed in 34 children (4-6 years old, weight: 16-68 kg) in whom major blood loss was expected during operation. Anaesthesia was induced with thiopentone, and then maintained with N2O/O2, fentanyl and pipecuronium. IPPV was used to maintain normocapnia. Heart rate, blood pressure, central venous pressure and core body temperature were monitored during haemodilution and throughout the surgery. A predetermined volume of blood to reduce hematocrit value to 30% was withdrawn in standard collection bags. In one child from Jehovah's Witness family hematocrit following haemodilution was only 20%. Every 1 ml of withdrawn blood was replaced with 1 ml of Haemaccel (Boehring, 32 children) or with 3 ml of isotonic crystalloid solution (PWE Polfa, 2 children). The blood lost during surgery was replaced with crystalloid solution and Haemaccel. Normovolemic loss of blood to haematocrit value of 20-24% was permitted. Retransfusion of collected blood was started when major bleeding was over, or when hematocrit decreased below 20-24%. Only 8 children needed homologous blood transfusion. Heart rate decreased significantly during haemodilution, while blood pressure remained stable. Low initial haematocrit and coagulopathy due to dilution of the plasma clotting factors were the limiting factors of the method. Partial thromboplastin time and plasma fibrinogen should be monitored throughout surgery, because the occurrence of coagulopathy promptly allows to initiate retransfusion of autologous blood.

Two cases of the "cannot ventilate, cannot intubate" scenario in children in view of recent recommendations.

We present two cases of a "cannot ventilate, cannot intubate" scenario in children in view of the latest guidelines for the management of unexpectedly difficult paediatric airways. Case 1 was a 5-year-old boy with Treacher-Collins syndrome who suffered gastric rupture due to gastric distension with oxygen during attempts to maintain oxygenation at the induction of anaesthesia. Difficulties in maintaining this patient's airways should be attributed to functional rather than anatomical obstruction, because no such problem occurred during subsequent anaesthetic inductions; therefore muscle relaxation would be helpful in this situation. In case 2, vecuronium was used in a 10-month-old infant scheduled for elective laryngoscopy because of stride due to vocal cord paralysis. Because of congenital maxillo-facial malformation, the infant could not be intubated, and ventilation via a face mask became difficult. Facing rapid deterioration of oxygenation, neuromuscular block was reversed with the use of sugammadex. The recovery of spontaneous respiration was almost immediate, and normal motor function returned within 90 s. Functional airway obstruction due to laryngospasm, insufficient depth of anaesthesia, or opioid-induced muscle rigidity with glottic closure can occur in a healthy child, as well as in a child with difficult airways, and requires clear concepts and therapeutic algorithms. Recent paediatric guidelines for the management of unexpectedly difficult airways stress the role of muscle relaxants in overcoming functional airway obstruction. The possibility of reversing neuromuscular block produced by rocuronium or vecuronium with sugammadex to awaken the patient adds to the safety of this algorithm.

Perioperative problems and treatment of a teenager with a juvenile angiofibroma refusing blood transfusion.

OBJECTIVES: Juvenile angiofibroma is a benign, non-encapsulated neoplasm, consisting of vascular and connective tissue. Its main feature is a local malignancy. In its clinical course it destroys adjoining structures, without metastasizing. It appears rarely, and is mainly found in boys at puberty. Among theories about the aetiology of juvenile angiofibroma, we must consider a haematoma-like lesion, an angioma with an extended fibrous component, or type of inflammatory allergic polyp. In the development of the lesion the participation of hormonal disorders on the pituitary gland-gonad axis is also suggested. According to the latest research, juvenile angiofibroma is regarded as a developmental defect, affecting the embryonic vascular network surrounding the sphenoid bone. METHODS: If the patient or his/her parents refuse blood transfusion and use of blood products, it is necessary to apply modifications in the routine perioperative treatment. In the case of the patient refusing blood and blood products transfusion because of their beliefs, it is possible to get consent to use different, highly processed products like albumins or a cryoprecipitate, as well as applying some blood-saving techniques. CONCLUSIONS: 1. Removal of juvenile angiofibroma with minimal bleeding is possible. 2. Applying erythropoietin and iron preparations prior to surgery increases erythropoiesis and reduces the risks in transfusion. 3. Applying intraoperative normovolaemic haemodilution is a safe method and allows avoidance of transfusion of blood-derived products.

Sevoflurane increases fade of neuromuscular response to TOF stimulation following rocuronium administration in children. A PK/PD analysis.

BACKGROUND: Sevoflurane enhances neuromuscular block produced by rocuronium, affecting not only single twitch response but also the response to high-frequency stimulation, increasing tetanic [or train-of-four (TOF)] fade. METHODS: We compared the degree of fade during spontaneous recovery from rocuronium-induced neuromuscular block in 24 children (3-11 years old, ASA groups I and II), anesthetized with nitrous oxide-sevoflurane (one MAC, endtidal concentration) or nitrous oxide-fentanyl. Neuromuscular transmission was monitored electromyographically (EMG), stimulating the ulnar nerve at the wrist with TOF, 2 Hz for 2 s, repeated at 20-s intervals and recording EMG potential from adductor pollicis brevis. Depression of the fourth twitch, T4, was used as a measure of fade. Following an intubating dose of rocuronium, 0.6 mgxkg(-1), continuous infusion of rocuronium was given to maintain stable 90-99% T1 depression. Plasma concentration of rocuronium was determined with high performance liquid chromatography with electrochemical detection (HPLC-EC) method at the moment of discontinuation of rocuronium infusion and 10, 20, 30, 40, 50, 60, and 75 min afterwards. A two compartment model was used for pharmacokinetic (PK) calculations. PK parameters were fixed and pharmacodynamic data were fitted to effect compartment model proposed by Sheiner. RESULTS: Sevoflurane reduced rocuronium concentration in effect compartment producing 50% inhibition of both T1 and T4 response and significantly delayed not only T1, but also T4 recovery. CONCLUSIONS: Potentiating effect of sevoflurane on rocuronium-induced neuromuscular block influences not only postsynaptic, but also the presynaptic part of the neuromuscular junction, enhancing fade of neuromuscular response to high-frequency stimulation. The intensity of this latter effect is clinically relevant.