John M. Bonvini

Protection of pharmacological postconditioning in liver surgery: results of a prospective randomized controlled trial.

Objectives:To elucidate the possible organ-protective effect of pharmacological postconditioning in patients undergoing liver resection with inflow occlusion. Background:Inflow occlusion reduces blood loss during liver transection in selected patients but is potentially harmful due to ischemia-reperfusion injury. Preventive strategies include the use of repetitive short periods of ischemia interrupted by a reperfusion phase (intermittent clamping), application of a short period of ischemia before transection (ischemic preconditioning), or pharmacological preconditioning before transection. Whether intervention after resection (postconditioning) may confer protection is unknown. Methods:A 3 arm, prospective, randomized trial was designed for patients undergoing liver resection with inflow occlusion to compare the effects of pharmacological postconditioning with the volatile anesthetic agent sevoflurane (n = 48), intermittent clamping (n = 50), or no protective intervention (continuous inflow occlusion, n = 17). Endpoints included peak serum aspartate transaminase level, postoperative complications, and hospital stay. All patients were intravenously anesthetized with propofol. In patients with postconditioning, propofol infusion was stopped upon reperfusion and replaced with sevoflurane for 10 minutes. Results:Compared with the control group, both postconditioning (P = 0.044) and intermittent clamping (P = 0.015) significantly reduced aspartate transaminase levels. The risk of complications was significantly decreased by postconditioning, odds ratio, 0.08 [95% confidence interval (CI), 0.02–0.36; P = 0.001]) and intermittent clamping, odds ratio, 0.50 [95% CI, 0.26–0.96; P = 0.038], compared with controls. Both interventions reduced length of hospital stay, postconditioning −4 days [95% CI, −6 to −1; P = 0.009], and intermittent clamping −2 days, [95% CI, −4 to 0; P = 0.019]. Conclusions:Pharmacological postconditioning reduces organ injury and postoperative complications. This easily applicable strategy should be used in patients with prolonged continuous inflow occlusion.

Bronchoaspiration: incidence, consequences and management

Aspiration is defined as the inhalation of oropharyngeal or gastric contents into the lower respiratory tract. Upon injury, epithelial cells and alveolar macrophages secrete chemical mediators, attracting and activating neutrophils, which in turn release proteases and reactive oxygen species, degrading the alveolocapillary unit. Aspiration can lead to a range of diseases such as infectious pneumonia, chemical pneumonitis or respiratory distress syndrome with significant morbidity and mortality. It occurs in approximately 3–10 per 10 000 operations with an increased incidence in obstetric and paediatric anaesthesia. Patients are most at risk during induction of anaesthesia and extubation, in particular in emergency situations. The likelihood of significant aspiration can be reduced by fasting, pharmacological intervention and correct anaesthetic management using a rapid sequence induction. Treatment of acid aspiration is by suctioning after witnessed aspiration; antibiotics are indicated in patients with aspiration pneumonia only. Steroids are not proven to improve outcome or reduce mortality. Patients with acute lung injury requiring mechanical ventilation should be ventilated using lung protective strategies with low tidal volumes and low plateau pressure values, attempting to limit peak lung distension and end-expiratory collapse.

Continuous spinal anesthesia/analgesia vs. single‐shot spinal anesthesia with patient‐controlled analgesia for elective hip arthroplasty

Background:  In total hip replacement surgery several anesthesiological techniques can be used. In this study we compared continuous spinal anesthesia (CSA) and postoperative analgesia vs. single‐shot spinal anesthesia (SPA) and postoperative patient‐controlled intravenous analgesia with morphine (SPA).

Platypnea–orthodeoxia syndrome in the elderly treated by percutaneous patent foramen ovale closure: A case series and literature review

BACKGROUND Platypnea-orthodeoxia syndrome (POS) is a rare clinical phenomenon, associating normal oxygen saturation in a supine position and arterial hypoxemia in an upright position. This pathology can be secondary to an intracardiac shunt, a pulmonary vascular shunt or a ventilation-perfusion mismatch. Cardiac POS occurs in the presence of a right-to-left cardiac shunt, most commonly through a patent foramen ovale (PFO). METHODS AND RESULTS From our single-center prospective database of percutaneous PFO closure we identified five patients (4 females, mean age: 77 ± 11 years) out of 224 (2.2%) patients with a PFO who presented with a POS of cardiac origin. Transthoracic and transoesophageal echocardiographic examinations revealed the underlying mechanisms of POS and the diagnosis was confirmed by right-and-left cardiac catheterization (RLC) and by measuring serial blood oxygen saturation in the pulmonary veins and left atrium in supine and upright positions. PFO was associated with atrial septal aneurysm and a persistent prominent Eustachian valve in 3 patients. All patients underwent a successful percutaneous PFO closure without any immediate or subsequent complications (mean follow-up of 24 ± 18 months). Immediately after the procedure, mean arterial oxygen saturation improved from 83% ± 3 to 93% ± 2 in an upright position and symptoms disappeared. CONCLUSION POS is a rare and under-diagnosed pathology that must be actively investigated in the presence of position-dependent hypoxemia. The diagnostic work-up must exclude other causes of hypoxemia and confirm the intracardiac shunt using either contrast echocardiography or RLC. For cardiac POS, percutaneous PFO closure is a safe and effective technique that immediately relieves orthodeoxia and patient symptoms.

Conditioning With Sevoflurane in Liver Transplantation: Results of a Multicenter Randomized Controlled Trial

Background During times of organ scarcity and extended use of liver grafts, protective strategies in transplantation are gaining importance. We demonstrated in the past that volatile anesthetics such as sevoflurane attenuate ischemia-reperfusion injury during liver resection. In this randomized study, we examined if volatile anesthetics have an effect on acute graft injury and clinical outcomes after liver transplantation. Methods Cadaveric liver transplant recipients were enrolled from January 2009 to September 2012 at 3 University Centers (Zurich/Sao Paulo/Ghent). Recipients were randomly assigned to propofol (control group) or sevoflurane anesthesia. Postoperative peak of aspartate transaminase was defined as primary endpoint, secondary endpoints were early allograft dysfunction, in-hospital complications, intensive care unit, and hospital stay. Results Ninety-eight recipients were randomized to propofol (n = 48) or sevoflurane (n = 50). Median peak aspartate transaminase after transplantation was 925 (interquartile range, 512–3274) in the propofol and 1097 (interquartile range, 540–2633) in the sevoflurane group. In the propofol arm, 11 patients (23%) experienced early allograft dysfunction, 7 (14%) in the sevoflurane one (odds ratio, 0.64 (0.20 to 2.02, P = 0.45). There were 4 mortalities (8.3%) in the propofol and 2 (4.0%) in the sevoflurane group. Overall and major complication rates were not different. An effect on clinical outcomes was observed favoring the sevoflurane group (less severe complications), but without significance. Conclusions This first multicenter trial comparing propofol with sevoflurane anesthesia in liver transplantation shows no difference in biochemical markers of acute organ injury and clinical outcomes between the 2 regimens. Sevoflurane has no significant added beneficial effect on ischemia-reperfusion injury compared to propofol.

Which Anesthesia Regimen Is Best to Reduce Morbidity and Mortality in Lung Surgery? A Multicenter Randomized Controlled Trial.

Background:One-lung ventilation during thoracic surgery is associated with hypoxia–reoxygenation injury in the deflated and subsequently reventilated lung. Numerous studies have reported volatile anesthesia–induced attenuation of inflammatory responses in such scenarios. If the effect also extends to clinical outcome is yet undetermined. We hypothesized that volatile anesthesia is superior to intravenous anesthesia regarding postoperative complications. Methods:Five centers in Switzerland participated in the randomized controlled trial. Patients scheduled for lung surgery with one-lung ventilation were randomly assigned to one of two parallel arms to receive either propofol or desflurane as general anesthetic. Patients and surgeons were blinded to group allocation. Time to occurrence of the first major complication according to the Clavien-Dindo score was defined as primary (during hospitalization) or secondary (6-month follow-up) endpoint. Cox regression models were used with adjustment for prestratification variables and age. Results:Of 767 screened patients, 460 were randomized and analyzed (n = 230 for each arm). Demographics, disease and intraoperative characteristics were comparable in both groups. Incidence of major complications during hospitalization was 16.5% in the propofol and 13.0% in the desflurane groups (hazard ratio for desflurane vs. propofol, 0.75; 95% CI, 0.46 to 1.22; P = 0.24). Incidence of major complications within 6 months from surgery was 40.4% in the propofol and 39.6% in the desflurane groups (hazard ratio for desflurane vs. propofol, 0.95; 95% CI, 0.71 to 1.28; P = 0.71). Conclusions:This is the first multicenter randomized controlled trial addressing the effect of volatile versus intravenous anesthetics on major complications after lung surgery. No difference between the two anesthesia regimens was evident.

Intrathecal hyperbaric 2% prilocaine versus 0.4% plain ropivacaine for same-day arthroscopic knee surgery: a prospective randomized double-blind controlled study

BackgroundShort-duration spinal anesthesia is a good option for ambulatory knee surgery. Hyperbaric 2% prilocaine has short onset and rapid recovery times and, therefore, may be well suited in this setting. The aim of this study was to compare the times to reach motor block, motor block resolution, and discharge from the postanesthesia care unit (PACU) between hyperbaric 2% prilocaine and 0.4% plain ropivacaine.MethodsIn this prospective randomized double-blind study, 140 patients (ages 18-80 yr and American Society of Anesthesiologists physical status I-II) scheduled for elective unilateral arthroscopic knee surgery lasting < 45 min were allocated to either 3 mL of 2% prilocaine (60 mg) or 3 mL of 0.4% plain ropivacaine (12 mg). Time to reach complete recovery of motor block, time to reach criteria for discharge, as well as side effects up to 48 hr after discharge were recorded.ResultsThe median (interquartile range [IQR]) time to recovery from the motor block was faster in the 2% prilocaine group compared with the 0.4% ropivacaine group (180 [169-240] min vs 240 [180-300] min, respectively; median difference, 60 min, 95% confidence interval (CI), 23 to 97 min; P = 0.036). The median [IQR] time to reach discharge criteria was similar between the two groups (330 [295-365] min vs, 335 [290-395] min; median difference 5 min, 95% CI, −25 to 35 min; P = 0.330). The incidence of side effects was low and similar in both groups. No case of transient neurologic symptoms occurred in either group.ConclusionThe recovery of motor block was faster after intrathecal administration of hyperbaric 2% prilocaine compared with 0.4% plain ropivacaine; however, discharge time was similar between the two groups. Both drugs showed a similar risk profile.RésuméContexteLa rachianesthésie de courte durée est une bonne option lorsqu’on pratique une chirurgie ambulatoire du genou. Le délai d’action de la prilocaïne 2 % hyperbare est court et son temps de récupération rapide; cet agent pourrait donc être adapté pour cette indication. L’objectif de cette étude était de comparer le temps jusqu’à installation du bloc moteur, jusqu’à résolution du bloc moteur, et jusqu’au congé de la salle de réveil entre la prilocaïne 2 % hyperbare et la ropivacaïne 0,4 %.MéthodeDans cette étude randomisée prospective à double insu, 140 patients (âgés de 18 à 80 ans et de statut physique I-II selon l’American Society of Anesthesiologists) devant subir une arthroscopie unilatérale du genou non-urgente d’une durée de moins de 45 minutes ont reçu soit 3 mL de prilocaïne 2 % (60 mg), ou 3 mL de ropivacaïne 0,4 % (12 mg). Le temps jusqu’à résolution complète du bloc moteur, le temps jusqu’à atteinte des critères nécessaires au congé, ainsi que les effets secondaires jusqu’à 48 h après le congé ont été enregistrés.RésultatsLe temps médian (écart interquartile [ÉIQ]) jusqu’à récupération du bloc moteur était plus court dans le groupe prilocaïne 2 % que dans le groupe ropivacaïne 0,4 % (180 [169-240] min vs. 240 [180-300] min, respectivement; différence médiane, 60 min, intervalle de confiance (IC) 95 %, 23 à 97 min; P = 0,036). Le temps médian [ÉIQ] jusqu’à atteinte des critères de congé était semblable dans les deux groupes (330 [295-365] min vs. 335 [290-395] min; différence médiane 5 min, IC 95 %, -25 à 35 min; P = 0,330). L’incidence d’effets secondaires était faible et semblable dans les deux groupes. Il n’y a pas eu de cas de symptôme neurologique transitoire.ConclusionLa récupération après un bloc moteur est plus courte après l’administration intrathécale de prilocaïne 2 % hyperbare comparativement à la ropivacaïne 0,4 %; toutefois, le temps jusqu’au congé était semblable dans les deux groupes. Le profil de risque des deux médicaments était semblable.

Poor responsiveness to antiplatelet drugs in acute coronary syndromes: clinical relevance and management

Cardiovascular diseases are the most common cause of mortality and morbidity in Western countries, accounting for more than 40% of total mortality. An optimal pharmacological management in these patients is of major importance and antiplatelet agents remain the cornerstone of acute coronary syndrome (ACS) therapy at hospital admission and during percutaneous coronary interventions (PCI). The recently described poor biological responses to aspirin and clopidogrel have been source of major concern, especially in era of drug eluting stent implantation. Indeed, insufficient platelet inhibition at the time of PCI has been consistently associated with an increased risk of complications and recurrence of ischemic events. Despite the lack of uniformly accepted definitions of aspirin and clopidogrel poor response, we sought to describe the current evidence and gaps in knowledge. While trials on the potential benefit of an increased antiplatelet maintenance dose after PCI have shown only marginal benefits, the strengthening of the initial antiplatelet regimens by additional loading doses of clopidogrel, by the administration of glycoprotein IIb/IIIa receptor inhibitors or phosphodiesterase inhibitors might further improve outcomes during ACS and PCI in patients with poor responsiveness to conventional dual antiplatelet therapy. Overall, tailoring the antiplatelet treatment on the basis of the individual biological response improves the short-term outcome after PCI. New and more potent antiplatelet drugs may overcome the clinical consequences of the poor response to antiplatelet agents.

Intraoperative adverse events during irreversible electroporation-a call for caution.

BACKGROUND Irreversible electroporation is increasingly used for treatment of solid tumors, but safety data remain scarce. This study aimed to describe intraoperative adverse events associated with irreversible electroporation in patients undergoing solid tumor ablation. METHODS We analyzed demographic and intraoperative data for patients (n = 43) undergoing irreversible electroporation for hepato-pancreato-biliary and retroperitoneal malignancies (2012 to 2015). Adverse events were defined as cardiac, surgical, or equipment-related. RESULTS Adverse events (n = 20, 47%) were primarily cardiac (90%, n = 18), including blood pressure elevation (77%, n = 14/18) and arrhythmia (16%, n = 7/43). All but one was managed medically, 1 patient with arrhythmia required termination of ablation. Bleeding and technical problems with the equipment occurred in 1 patient each. Multivariable analysis revealed previous cardiovascular disease and needle placement close to the celiac trunk associated with increased likelihood for cardiac events. CONCLUSIONS Intraoperative cardiac adverse events are common during irreversible electroporation but rarely impair completion of the procedure.

Late Post-Conditioning with Sevoflurane after Cardiac Surgery - Are Surrogate Markers Associated with Clinical Outcome?

Introduction In a recent randomized controlled trial our group has demonstrated in 102 patients that late post-conditioning with sevoflurane performed in the intensive care unit after surgery involving extracorporeal circulation reduced damage to cardiomyocytes exposed to ischemia reperfusion injury. On the first post-operative day the sevoflurane patients presented with lower troponin T values when compared with those undergoing propofol sedation. In order to assess possible clinical relevant long-term implications in patients enrolled in this study, we performed the current retrospective analysis focusing on cardiac and non-cardiac events during the first 6 months after surgery. Methods All patients who had successfully completed the late post-conditioning trial were included into this follow-up. Our primary and secondary endpoints were the proportion of patients experiencing cardiac and non-cardiac events, respectively. Additionally, we were interested in assessing therapeutic interventions such as initiation or change of drug therapy, interventional treatment or surgery. Results Of 102 patients analyzed in the primary study 94 could be included in this follow-up. In the sevoflurane group (with 41 patients) 16 (39%) experienced one or several cardiac events within 6 months after cardiac surgery, in the propofol group (with 53 patients) 19 (36%, p=0.75). Four patients (9%) with sevoflurane vs. 7 (13%) with propofol sedation had non-cardiac events (p=0.61). While a similar percentage of patients suffered from cardiac and/or non-cardiac events, only 12 patients in the sevoflurane group compared to 20 propofol patients needed a therapeutic intervention (OR: 0.24, 95% CI: 0.04-1.43, p=0.12). A similar result was found for hospital admissions: 2 patients in the sevoflurane group had to be re-admitted to the hospital compared to 8 in the propofol group (OR 0.23, 95% CI: 0.04-1.29, p=0.10). Conclusions Sevoflurane does not seem to provide protection with regard to the occurrence of cardiac and non-cardiac events in the 6-month period following cardiac surgery with the use of extracorporeal circulation. However, there was a clear trend towards fewer interventions (less need for treatment, fewer hospital admissions) associated with sevoflurane post-conditioning in patients experiencing any event. Such results might encourage launching large multicenter post-conditioning trials with clinical outcome defined as primary endpoint.