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

Clinical concentrations of morphine are cytotoxic on proliferating human fibroblasts in vitro

BACKGROUND: Morphine and other opioids are routinely used systemically and as wound infusions in the postoperative period. Their effect on wound and fracture healing remains unclear. OBJECTIVE: The primary outcome was to assess the potential cytotoxicity of clinically relevant concentrations of morphine on human fibroblasts. DESIGN: Laboratory in-vitro study. SETTING: Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich. MATERIALS: Monolayers of human fibroblasts. INTERVENTION(S): Exposure of human fibroblast monolayers to several concentrations of morphine, for different periods of time, with and without an artificially induced inflammatory process. MAIN OUTCOME MEASURES: Cell count, cell viability, cell proliferation and apoptosis. RESULTS: A concentration, time and exposure-dependent cytotoxic effect of morphine-mediated apoptosis was observed. Simulated inflammatory conditions seemed to lessen toxic effects. CONCLUSION: Cytotoxic effects of morphine are exposure, time and concentration dependent. Simulating aspects of inflammatory conditions seems to increase resistance to morphine cytotoxicity especially in the presence of higher concentration and longer exposure times

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

Sevoflurane preconditioning protects from posttransplant injury in mouse lung transplantation

BACKGROUND: Although sevoflurane (Sevo) had been shown to ameliorate posttransplant injury in various organs, data available are inconsistent, particularly in the context of lung transplantation (Tx). We here investigated if preconditioning by Sevo can protect from posttransplant injury regarding both, primary graft dysfunction (PGD) and acute rejection (AR) after experimental lung Tx, thereby focusing on two important clinical outcome parameters. MATERIALS AND METHODS: Three experimental approaches were used: (1) BALB/c mice were preconditioned for 2 h with Sevo or a fentanyl cocktail (Control; n = 10); (2) syngeneic (Syn) mouse lung Tx (C57BL/6) with a Sevo-preconditioned graft followed by 18 h storage to mimic PGD (Syn-Tx, n = 12) versus controls (fentanyl cocktail); and (3) allogeneic (Allo) Tx (BALB/c, donor; C57BL/6, recipient) to mimic AR (Allo-Tx, n = 12) versus controls (fentanyl cocktail). Syn-Tx grafts were harvested on Day 1, Allo-Tx grafts on Day 3 and analyzed for histology, immunohistochemistry, blood gas analysis, and inflammatory cytokines (enzyme-linked immunosorbent assay or reverse transcription polymerase chain reaction). RESULTS: Evaluating the preconditioning effect of Sevo only showed significantly better oxygenation (P = 0.03) and a tendency toward lower levels of lung tissue messenger RNA for tumor necrosis factor-α. In Syn-Tx recipients, the Sevo group had histologically a tendency toward an attenuation of PGD and showed significantly lower levels of interleukin 6 (P = 0.01) in plasma, but higher levels of interleukin 10 (P < 0.01) in lungs. Allo-Tx grafts in Sevo Tx recipients showed attenuated AR with histologically significantly lower rejection scores (P = 0.03), fewer classical macrophages (F4/80+; P < 0.01), but more anti-inflammatory activated macrophages (M2, CD206+; P < 0.01). Functionally, the Sevo group had a tendency toward improved oxygenation. CONCLUSIONS: We demonstrated that Sevo preconditioning has protective effects on lung transplants in both, PGD and AR. The observed amelioration may be attributed to suppressed inflammatory cytokines during PGD and the induction of alternatively activated macrophages during AR. These promising data could set the base for using Sevo preconditioning in donor lungs for a human trial

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

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)

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

BACKGROUND Short-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. METHODS In 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. RESULTS The 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. CONCLUSION The 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

Inflammation reduces osteoblast cytotoxicity induced by diclofenac: An in vitro study

BACKGROUND Diclofenac and other NSAIDs are routinely used in the postoperative period. Their effect on fracture healing remains unclear and controversial. OBJECTIVE The primary outcome was to assess the potential cytotoxicity of clinically relevant concentrations of diclofenac on human osteoblasts. DESIGN Laboratory in vitro study. SETTING Institute of Physiology, Zurich, Center for Integrative Human Physiology, University of Zurich. MATERIALS Monolayers of human osteoblasts. INTERVENTIONS Exposure of human osteoblast monolayers to several concentrations of diclofenac, for different periods of time, with and without an artificially induced inflammatory process. MAIN OUTCOME MEASURES Cell count, cell viability, cell proliferation and apoptosis. RESULTS A concentration-mediated, time and exposure dependent cytotoxic effect of diclofenac-mediated apoptosis was observed. Stimulated inflammatory conditions seemed to reduce toxic effects. CONCLUSION Cytotoxic effects of diclofenac are exposure, time and concentration dependent. Simulating aspects of inflammatory conditions seems to increase resistance to diclofenac cytotoxicity, especially in the presence of higher concentration and longer exposure time

There is no evidence that carbon dioxide-enriched oxygen before apnea affects the time to arterial desaturation, but it might improve cerebral oxygenation in anesthetized obese patients: a single-blinded randomized crossover trial

Purpose Carbon dioxide (CO$_{2}$) increases cerebral perfusion. The effect of CO$_{2}$ on apnea tolerance, such as after anesthesia induction, is unknown. This study aimed to assess if cerebral apnea tolerance can be improved in obese patients under general anesthesia when comparing O$_{2}$/Air (95%O$_{2}$) to O$_{2}$/CO$_{2}$ (95%O$_{2}$/5%CO$_{2}$). Methods In this single-center, single-blinded, randomized crossover trial, 30 patients 18–65 years, with body mass index > 35 kg/m$^{2}$, requiring general anesthesia for bariatric surgery, underwent two apneas that were preceded by ventilation with either O$_{2}$/Air or O$_{2}$/CO$_{2}$ in random order. After anesthesia induction, intubation, and ventilation with O$_{2}$/Air or O$_{2}$/CO$_{2}$ for 10 min, apnea was performed until the cerebral tissue oxygenation index (TOI) dropped by a relative 20% from baseline (primary endpoint) or oxygen saturation (SpO$_{2}$) reached 80% (safety abortion criterion). The intervention was then repeated with the second substance. Results The safety criterion was reached in all patients before cerebral TOI decreased by 20%. The time until SpO$_{2}$ dropped to 80% was similar in the two groups (+ 6 s with O$_{2}$/CO$_{2}$, 95%CI -7 to 19 s, p = 0.37). Cerebral TOI and PaO$_{2}$ were higher after O$_{2}$/CO$_{2}$ (+ 1.5%; 95%CI: from 0.3 to 2.6; p = 0.02 and + 0.6 kPa; 95%CI: 0.1 to 1.1; p = 0.02). Conclusion O$_{2}$/CO$_{2}$ improves cerebral TOI and PaO$_{2}$ in anesthetized bariatric patients. Better apnea tolerance could not be confirmed