Association between probiotics and enteral nutrition in an experimental acute pancreatitis model in rats.

BACKGROUND/OBJECTIVES: Recently, a randomized controlled trial showed that probiotic prophylaxis was associated with an increased mortality in enterally fed patients with predicted severe pancreatitis. In a rat model for acute pancreatitis, we investigated whether an association between probiotic prophylaxis and enteral nutrition contributed to the higher mortality rate. METHODS: Male Sprague-Dawley rats were allocated to four groups: 1) acute pancreatitis (n = 9), 2) acute pancreatitis and probiotic prophylaxis (n = 10), 3) acute pancreatitis and enteral nutrition (n = 10), and 4) acute pancreatitis, probiotic prophylaxis and enteral nutrition (n = 11). Acute pancreatitis was induced by intraductal glycodeoxycholate and intravenous cerulein infusion. Enteral nutrition, saline, probiotics and placebo were administered through a permanent jejunal feeding. Probiotics or placebo were administered starting 4 days before induction of pancreatitis and enteral nutrition 1 day before start until the end of the experiment, 6 days after induction of pancreatitis. Tissue samples and body fluids were collected for microbiological and histological examination. RESULTS: In all animals, serum amylase was increased six hours after induction of pancreatitis. After fulfilling the experiment, no differences between groups were found in histological severity of pancreatitis, degree of discomfort, weight loss, histological examination of small bowel and bacterial translocation (all p > 0.05). Overall mortality was 10% without differences between groups (p = 0.54). CONCLUSION: No negative association was found between prophylactic probiotics and enteral nutrition in acute pancreatitis. No new clues for a potential mechanism responsible for the higher mortality and bowel ischaemia in the PROPATRIA study were found.

Mechanical ventilation of mice under general anesthesia during experimental procedures.

Mechanical ventilation is frequently used in patients under general anesthesia during invasive procedures. Invasive animal experiments similarly require the maintenance of normal hemodynamic and pulmonary parameters during long-term general anesthesia. The authors describe a method for mechanical ventilation of mice. Mice were ventilated and monitored for up to 8 h of general anesthesia during surgery. Hemodynamic and pulmonary parameters remained within the normal ranges. The authors believe that this ventilation technique can be of great value for experimental procedures in mice that require general anesthesia.

Reversal of rocuronium-induced neuromuscular block by sugammadex is independent of renal perfusion in anesthetized cats.

PURPOSE: Sugammadex is a selective relaxant binding agent designed to encapsulate the aminosteroidal neuromuscular blocking agent rocuronium, thereby reversing its effect. Both sugammadex and the sugammadex-rocuronium complex are eliminated by the kidneys. This study investigated the effect of sugammadex on recovery of rocuronium-induced neuromuscular block in cats with clamped renal pedicles, as a model for acute renal failure. METHODS: Twelve male cats were divided into two groups and anesthetized with medetomidine, ketamine, and alpha-chloralose. The cats were intubated and ventilated with a mixture of oxygen and air. Neuromuscular monitoring was performed by single twitch monitoring. Rocuronium 0.5 mg/kg i.v. was administered. After spontaneous recovery from neuromuscular block, both renal pedicles were ligated. A second dose of rocuronium 0.5 mg/kg i.v. was given. One minute after disappearance of the twitches, in Group 1 placebo (0.9% saline) and in Group 2 sugammadex 5.0 mg/kg i.v. was administered. Onset time, duration of neuromuscular block, and time to recovery to 25, 50, 75, and 90% were determined. RESULTS: After renal pedicle ligation, sugammadex reversed rocuronium-induced neuromuscular block significantly faster than spontaneous recovery. Mean time (SEM) to 90% recovery of the twitch response was 4.7 (0.25) min (Group 2) versus 31.1 (5.0) min (Group 1) (p < 0.0001). No signs of recurrence of neuromuscular block were observed for 90 min after complete twitch restoration. Sugammadex caused no significant cardiovascular effects. CONCLUSION: Sugammadex rapidly and effectively reversed rocuronium-induced neuromuscular block in anesthetized cats, even when both renal pedicles were ligated and renal elimination of the drugs was no longer possible.

Sugammadex reverses neuromuscular block induced by 3-desacetyl-vecuronium, an active metabolite of vecuronium, in the anaesthetised rhesus monkey.

BACKGROUND AND OBJECTIVE: 3-Desacetyl-vecuronium is an active metabolite of the neuromuscular blocking agent (NMBA) vecuronium, which might lead to residual paralysis after prolonged administration of vecuronium in critically ill patients with renal failure. This study investigated the ability of sugammadex to reverse 3-desacetyl-vecuronium-induced neuromuscular block (NMB) in the anaesthetised rhesus monkey. METHODS: Experiments were performed in anaesthetised female rhesus monkeys. After bolus intravenous injection of vecuronium (n = 8) or 3-desacetyl-vecuronium (n = 8) 10 µg kg(-1) (ED90), a continuous infusion of the same NMBA was started to maintain the first twitch of the train-of-four (TOF) at 10% of baseline value. The infusion was stopped and NMB recovered spontaneously. The procedure was repeated, but immediately after stopping the infusion, an intravenous bolus dose of sugammadex 0.5 or 1.0 mg kg(-1) was given. For each NMBA, four placebo experiments were performed, in which the second recovery from NMB was also spontaneous. For all experiments, time to recovery of the TOF ratio to 90% was retrieved. RESULTS: After administration of sugammadex for reversal of 3-desacetyl-vecuronium-induced NMB, recovery was significantly faster than spontaneous recovery. Mean time to recovery of TOF to 90% was 3.2 min (sugammadex 0.5 mg kg(-1)) and 2.6 min (1.0 mg kg(-1)), compared to spontaneous recovery (17.6 min). For vecuronium-induced NMB, mean time to recovery of TOF to 90% was 17.1 min (0.5 mg kg(-1)) and 4.6 min (1.0 mg kg(-1)), compared to spontaneous recovery (23.4 min). CONCLUSION: Sugammadex rapidly and effectively reversed 3-desacetyl-vecuronium-induced NMB in the rhesus monkey, at a lower dose than that needed to reverse vecuronium-induced NMB.

Reversal of profound rocuronium neuromuscular blockade by sugammadex in anesthetized rhesus monkeys.

BACKGROUND: Reversal of neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a synthetic gamma-cyclodextrin derivative. The current study determined the feasibility of reversal of rocuronium-induced profound neuromuscular blockade with sugammadex in the anesthetized rhesus monkey using train-of-four stimulation. METHODS: Four female rhesus monkeys each underwent three experiments. In each experiment, first, a 100-microg/kg dose of rocuronium was injected and spontaneous recovery was monitored. After full recovery, a 500-microg/kg dose of rocuronium was injected. Up to this point, all three experiments in a single monkey were identical. One minute after this rocuronium injection, either one of the two tested dosages of sugammadex (1.0 or 2.5 mg/kg) was injected or saline was injected. RESULTS: Injection of 100 microg/kg rocuronium resulted in a mean neuromuscular blockade of 93.0% (SD = 4%), and profound blockade was achieved by injection of 500 microg/kg. In all experiments, a 100% neuromuscular blockade was achieved at this dose. After injection of the high rocuronium dose, the 90% recovery of the train-of-four ratio took 28 min (SD = 7 min) after saline, 26 min (SD = 9.5 min) after 1 mg/kg sugammadex, and 8 min (SD = 3.6 min) after 2.5 mg/kg sugammadex. Signs of residual blockade or recurarization were not observed. Injection of sugammadex had no significant effects on blood pressure or heart rate. CONCLUSIONS: Chemical encapsulation of rocuronium by sugammadex is a new therapeutic mechanism allowing effective and rapid reversal of profound neuromuscular blockade induced by rocuronium in anesthetized rhesus monkeys.