Comparison of neostigmine vs. sugammadex for recovery of muscle function after neuromuscular block by means of diaphragm ultrasonography in microlaryngeal surgery: A randomised controlled trial.

BACKGROUND: Postoperative residual curarisation (PORC) is a risk directly related to the use of neuromuscular blocking agents during surgical procedures. Acceleromyography is distressing for conscious patients when assessing PORC. Diaphragm ultrasonography could be a valid alternative. OBJECTIVES: The primary objective was to achieve a 28% lower incidence of PORC in patients who, after rocuronium administration, received neostigmine or sugammadex at 30 min after surgery. To assess PORC, diaphragm ultrasonography was used, and thickening fractioning [the difference of thickness at the end of inspiration (TEI) and at the end of expiration (TEE), normalised for TEE (TEI - TEE/TEE)] was measured. PORC was defined as thickening fractioning of 0.36 or less. The secondary object was the comparison, in the two treatment groups, of the return to baseline thickening fractioning at 30 min after surgery (ΔTF30). DESIGN: Randomised, double-blind, single-centre study. SETTING: University Hospital Careggi, Florence, Italy. PATIENTS: Patients of American Society Anesthesiologists' physical status 1 or 2, 18 to 80 years, receiving rocuronium during microlaryngeal surgery. INTERVENTIONS: At the end of surgery participants were randomised to receive neostigmine (NEO group) or sugammadex (SUG group) as the reversal drug. Thickening fractioning and ΔTF30 were evaluated at baseline and at 0, 10 and 30 min after surgery. MAIN OUTCOME MEASURES: TEE and TEI at each time point. RESULTS: A total of 59 patients with similar demographic characteristics were enrolled. An association between lack of recovery (thickening fractioning ≤0.36) and drug treatment was only observed at 0 min (SUG vs. NEO, P < 0.05). Concerning ΔTF, at 30 min more patients in the SUG group returned to baseline than those in the NEO group (P < 0.001), after adjusting for side (P = 0.52), baseline thickening fractioning (P < 0.0001) and time of measurement (P < 0.01). CONCLUSION: We found an early (0 min) but not long-lasting (30 min) association between diaphragm failure and treatment allocation; a full recovery in baseline diaphragm function was observed only in patients receiving sugammadex. We cannot exclude that further differences have not been found due to interpatients variability in assessing diaphragm contractility by ultrasonography. TRIAL REGISTRATION: EudraCT Identifier: 2013-004787-62, Clinicaltrials.gov Identifier: NCT02698969.

Changes in ceftriaxone pharmacokinetics/pharmacodynamics during the early phase of sepsis: a prospective, experimental study in the rat.

BACKGROUND: Sepsis is characterized by the loss of the perm-selectivity properties of the glomerular filtration barrier (GFB) with consequent albuminuria. We examined whether the pharmacokinetics-pharmacodynamics (PK/PD) of ceftriaxone (CTX), an extensively protein-bound 3rd generation cephalosporin, is altered during early sepsis and whether an increase in urinary loss of bound-CTX, due to GFB alteration, can occur in this condition. METHODS: A prospective, experimental, randomized study was carried out in adult male Sprague-Dawley rats. Sepsis was induced by cecal ligation and puncture (CLP). Rats were divided into two groups: Sham-operated and CLP. CTX (100 mg i.p., equivalent to 1 g dose in humans) was administered in order to measure plasma and lung CTX concentrations at several time-points: baseline and 1, 2, 4 and 6 h after administration. CTX was measured by High Performance Liquid Chromatography (HPLC). The morphological status of the sialic components of the GFB barrier was assessed by lectin histo-chemistry. Monte Carlo simulation was performed to calculate the probability of target attainment (PTA >90%) for 80 and 100% of Tfree > minimum inhibitory concentration (MIC) for 80 and 100% of dosing interval. MEASUREMENTS AND MAIN RESULTS: After CLP, sepsis developed in rats as documented by the growth of polymicrobial flora in the peritoneal fluid (≤1 × 101 CFU in sham rats vs 5 × 104-1 × 105 CFU in CLP rats). CTX plasma concentrations were higher in CLP than in sham rats at 2 and 4 h after administration (difference at 2 h was 47.3, p = 0.012; difference at 4 h was 24.94, p = 0.004), while lung penetration tended to be lower. An increased urinary elimination of protein-bound CTX occurred (553 ± 689 vs 149 ± 128 mg/L, p < 0.05; % of bound/total CTX 22 ± 6 in septic rats vs 11 ± 4 in sham rats, p < 0.01) and it was associated with loss of the GFB sialic components. According to Monte Carlo simulation a PTA > 90% for 100% of the dosing interval was reached neither for sham nor CLP rats using MIC = 1 mg/L, the clinical breakpoint for Enterobacteriacee. CONCLUSIONS: Sepsis causes changes in the PK of CTX and an alteration in the sialic components of the GFB, with consequent loss of protein-bound CTX. Among factors that can affect drug pharmacokinetics during the early phases of sepsis, urinary loss of both free and albumin-bound antimicrobials should be considered.

Minocycline but not tigecycline is neuroprotective and reduces the neuroinflammatory response induced by the superimposition of sepsis upon traumatic brain injury.

OBJECTIVE: The development of sepsis in patients with traumatic brain injury increases mortality, exacerbates morphological and functional cerebral damage, and causes persistent neuroinflammation, including microglial activation. The administration of antibiotics possessing both antimicrobial and immunomodulatory activity might attenuate both sepsis and posttraumatic cerebral inflammation. We compared the potential therapeutic efficacy of two tetracyclines, minocycline and the newer generation tigecycline, on functional neurobehavioral impairment and regional histopathological damage in an experimental model of combined traumatic brain injury and sepsis. DESIGN: Prospective, experimental animal study. SETTING: University Research Laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Controlled cortical impact was used to induce traumatic brain injury and cecal ligation and puncture for sepsis. Immediately following injury, animals were treated with minocycline (45 mg/kg intraperitoneal), tigecycline (7.5 mg/kg intraperitoneal), or saline every 12 hours for 3 days. MEASUREMENTS AND MAIN RESULTS: The development of sepsis and cerebral inflammatory response were evaluated, respectively, by 1) growth of peritoneal microorganisms and clinical variables and 2) tumor necrosis factor-α expression in the perilesional cortex. To assess posttraumatic outcome, vestibulomotor and cognitive function were evaluated at different time points for 14 days post injury whereupon animals were killed and cerebral tissue analyzed for lesion volume, regional hippocampal (CA1/CA3) cell death, and microglial activation in the perilesional cortex, lesion core zone, and choroid plexus. Treatment with both antibiotics reduced microorganism growth, body weight loss, and mortality but had no effect on vestibulomotor or cognitive function. Minocycline alone attenuated postinjury cortical lesion volume, hippocampal CA3 neuronal cell loss, tumor necrosis factor-α expression, and the extent of microglial activation and infiltration. CONCLUSIONS: The significantly heightened mortality caused by the superimposition of sepsis upon traumatic brain injury can be reduced by administration of both antibiotics but only minocycline can decrease the extent of cell death in selectively cortical and hippocampal brain regions, via, in part, a reduction in cerebral inflammation.

Postoperative pain after vitreo-retinal surgery is influenced by surgery duration and anesthesia conduction.

BACKGROUND: The control of postoperative pain (POP) is a key component of perioperative care. POP after vitreo-retinal surgery (VRS) has been under-investigated, and its incidence remains elusive. METHODS: In order to assess POP after VRS, the associated risk factors and efficacy of the analgesic protocol in use at our institution, we made a one-year retrospective study on patients undergoing VRS. Patients aged >18 years, ASA Class I-III undergoing VRS entered the study. POP was evaluated by measuring a Numerical Rating Scale (NRS), and analgesic consumption. RESULTS: A total of 782 patients entered the study. Patients received locoregional (LRA) or general anesthesia (GA) with supplemental block. Twenty-two percent of patients needed analgesics (acetaminophen in 97% of cases), mostly between two and six hours after surgery. The univariate analysis showed a positive association between POP and duration of surgery (P<0.0001) and glaucoma (P=0.04), and a negative association with age (P=0.008), analgesic administration at the end of surgery (P=0.005) and the intraoperative administration of remifentanil for surgery under LRA (P=0.02); sedation to execute the block for LRA did not reduce POP. Patients treated with GA with supplemental block had less pain compared to those treated with LRA with/without remifentanil (P=0.03, P=0.002, respectively). The multivariate analysis confirmed a positive correlation between POP and duration of surgery (P=0.0007) and a negative correlation with the intraoperative remifentanil administration during LRA (P=0.04), and with GA with supplemental block (P=0.01). CONCLUSIONS: The incidence of POP after VRS is low but not absent, especially for long procedures, it does not require postoperative opioids and can be modified by anesthesiologic choices.