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.

Stuve Wiedemann syndrome and related syndromes: case report and possible anesthetic complications.

Stuve Wiedemann syndrome (SWS) is an autosomal recessively inherited syndrome which is characterized by bowing of the long bones, camptodactyly, facial dysmorphism, hypotonia, feeding and swallowing difficulties, and respiratory distress. In most cases episodes of unexplained hyperthermia are present. Patients with SWS can develop hyperthermia in conjunction with anesthesia and surgery, and a relationship has been suggested between the syndrome and malignant hyperthermia. We describe a 3-year-old child diagnosed with SWS to whom we administered general anesthesia during the removal of a corneal ulcer and dilatation of the lacrimal duct. Our patient had received, uncomplicated, inhalational anesthesia five times previously for different operations. There were no anesthesia-related complications in the present or previous perioperative periods. On one occasion the patient developed mild postoperative hyperthermia. We believe that this hyperthermia is different from the specific disorder of malignant hyperthermia and that sevoflurane can be safely used in patients with SWS. We also describe symptomatically related syndromes and their theoretical risks for anesthesia.

Isoflurane anesthesia is a valuable alternative for alpha-chloralose anesthesia in the forepaw stimulation model in rats.

Isoflurane (ISO) can be a valuable alternative for alpha-chloralose (ACL) anesthesia in functional MRI (fMRI) studies. Therefore, we compared the efficacy of the blood oxygen level dependent (BOLD) effect in fMRI studies during ISO and ACL anesthesia sequentially in the same animals. After non-invasive instrumentation for ventilation and monitoring, series of T2* weighted MR images were acquired during forepaw stimulation, first under ISO, then followed by ACL anesthesia. The results demonstrated that ISO and ACL were both suitable to perform this fMRI experiment. The center of activation was at the same stereotactic position for both anesthetics and matched the primary somatosensory cortex (S1). Under the applied conditions, the BOLD response during ISO anesthesia declined in magnitude during the first stimulation period, as compared to ACL. From this study, we conclude that since ISO has several positive properties in comparison to ACL, including fast pharmacokinetics and suitability for repeated measurements, it is a valuable alternative for anesthesia in fMRI studies of rats.

Sex, age, and genetics in anesthesia.

PURPOSE OF REVIEW: Pharmacology is one of the corner stones of anesthesia. Outcome of anesthesia is related, in part, to both pharmacodynamics and pharmacokinetics of anesthetic drugs. Recent developments have indicated that among individuals, major differences exist in pharmacological effects. In this regard, sex, age, and genetic profile are increasingly considered to be of importance. RECENT FINDINGS: For a number of anesthetic drugs, it has been demonstrated that sex differences influence their effects and thus can alter the outcome of anesthesia. Also other genetically determined differences than sex are important. SUMMARY: In the future, it is expected that an individual's pharmacological needs will be based on age, sex, and genomics.

Teamwork and the legal and ethical responsibility of the anaesthetist.

PURPOSE OF REVIEW: Anaesthetists are members of the operating team. Although the surgeons usually consider themselves to be the leaders of the team, all members, including the anaesthetist, have their own legal, ethical and professional responsibilities. RECENT FINDINGS: Good communication and sharing responsibility are characteristics of teamwork. Many factors can affect team functioning: training differences, social status, differences in responsibility, gender, age and culture, among others. An increasing number of individuals are involved in modern treatment due to limited working hours and increasing subspecialization, which complicates collaboration. Not all participants have the same perception of the team structure and its operation. Multidisciplinary, well designed training programmes are needed. SUMMARY: Anaesthetists have to be more aware of their position in the care team and pay more attention to their legal, ethical and professional responsibilities.

Anesthesia in the patient for awake craniotomy.

PURPOSE OF REVIEW: This review summarizes the current anesthetic management of patients undergoing craniotomies in the awake state. RECENT FINDINGS: As the practice of neurosurgery has moved towards less invasive procedures the need for prolonged, deep general anesthesia has decreased. Since brain mapping and neurophysiologic testing is an integral part of many neurosurgical techniques, the need to provide sufficient analgesia and sedation without interference with electrophysiologic monitoring is also essential. SUMMARY: A safe and acceptable analgesic/amnestic state for these procedures can be provided by the use of dexmedetomidine, with or without the addition of remifentanil.

Conflicts in the operating theatre.

PURPOSE OF REVIEW: Quality and safety of healthcare depend on team performance. Conflicts decrease team performance. A number of studied factors involved in the development and solution of conflicts are discussed. RECENT FINDINGS: An operating team consists of individuals, with specific roles requiring specific expertise and skills, performing interdependent tasks with patient treatment as a common goal. Teams are prone to conflicts: a dispute, disagreement or difference of opinion related to patient management, requiring some decision or action. Many factors determine the character of the conflicts, and these vary between different countries, hospitals and teams. Factors include culture, professional social status, personality of members, etc. Conflicts can induce innovation, but can also result in job dissatisfaction. They even can affect the functioning of the hospital. On average, four conflicts can be observed per operation, which are mostly solved immediately. Communication in an open atmosphere is a major issue in dealing with conflicts. If conflicts are unresolved they grow into relationship conflicts, which are difficult to handle. Understanding the factors that contribute to the conflict is important for mediators. Most conflicts arise about theatre management, case acceptation, unexpected changes in the team or incapability of one of its members. SUMMARY: There are many possible inductors of conflicts. Conflicts should be immediately resolved by open communication and respectful discussion.

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.

Interleukin-6 and perioperative thermoregulation and HPA-axis activation.

Surgery is followed by an acute-phase response, including hypothalamo-pituitary-adrenal (HPA)-axis activation and fever. Considering its physiological properties and its behaviour in plasma after stress and surgery, the pro-inflammatory cytokine interleukin (IL)-6 is a putative candidate in eliciting these stress-related symptoms. However, evidence for this hypothesis is lacking. Rats subjected to individual psychological stress for 1h were injected intraperitoneally with saline or 3.33 microg per 100g rat neutralizing antibodies against rat IL-6. Thereafter, the single-housed rats were anaesthetized for 25 min, with or without undergoing a laparotomy. Intermittently, oesophageal temperatures were measured at defined time points. A parallel group of rats undergoing the same study protocol were decapitated, at time points when body temperatures differed, to obtain blood for measurement of plasma adrenocorticotropic hormone and corticosterone. Individual housing resulted in hyperthermia. Antibodies against IL-6 accelerated normalization of body temperature after individualizing stress, limited postoperative hyperthermia after laparotomy, but accentuated hyperthermia after anaesthesia alone. Antibody administration was not able to significantly influence the plasma hormone levels during any experiment. The present study indicates that IL-6 is a thermoregulatory factor during psychological, anaesthesiological and surgical stress, but the cytokine does not participate in HPA-axis activation until 6h after anaesthesia or surgery. A dose-finding study with antibodies against IL-6 ought to further identify the degree of contribution of IL-6 to perioperative thermoregulation.

The role of interleukin-6 in nociception and pain.

IMPLICATIONS: That IL-6 is an interesting target in the study of pain is underscored by its biomolecular properties, its localization after experimental pain, and its modulating effect on pain after administration.

End-of-life decisions during intensive care treatment.

PURPOSE OF REVIEW: End-of-life decisions play an important role in the intensive care unit. This review discusses the most important studies on end-of-life decisions published from October 2001 to October 2002. RECENT FINDINGS: Refusal of admission to the intensive care unit in itself is frequently an end-of-life decision. However, some patients survive rejection. The main end-of-life decisions during intensive care unit stay are withholding or withdrawal of therapy. Some patients have do-not-resuscitate orders on admittance to a unit. The effect of family participation and involvement of other caregivers in such decisions has been extensively studied. Such participation can lead to anxiety and depression in the family. A procedural guideline for decision making is of clinical interest. The background of physicians plays an important role. Terminal sedation and analgesia play an important role in execution of end-of-life decisions. During intensive care unit admission there is a continuous change in circumstances, which causes continuous differences in the wishes of the patients and relatives. The small contribution of the cost of the last days of life to total healthcare cost was reconfirmed. SUMMARY: The new studies put emphasis on the facts that all care providers should participate in the decision and that communication with surrogates is of extreme importance. Many valid points from other medical fields also apply to the intensive care unit situation.

Time-course of action of rocuronium 0.3 mg.kg-1 in children with and without endstage renal failure.

BACKGROUND: The time-course of the neuromuscular effects of rocuronium 0.3 mg.kg-1 during nitrous oxide-halothane anaesthesia in children with and without renal failure is unknown. This study compared the neuromuscular blocking effects in these groups. METHODS: The study was approved by the Hospital Ethical Committee. In the control group, 14 healthy children without renal disease were scheduled for various elective surgical procedures. Sixteen children with endstage renal failure, 14 of whom were already on renal dialysis, were scheduled for (re)placement of dialysis catheters (n=14) or for renal transplantation (n=2). Anaesthesia was induced and maintained with halothane and nitrous oxide in oxygen. Acceleromyographic thumb adduction after supramaximal ulnar nerve stimulation was recorded using train-of-four stimulation every 15 s. The onset time, the time to recovery of the first twitch to 25% or 75% and to recovery of a train-of-four ratio of 0.7 after rocuronium 0.3 mg.kg-1 were measured. Statistical analysis was performed with Student's t-test. P < 0.05 was considered statistically significant. RESULTS: The onset time was longer in children with renal failure (139 s, SD=71) than in control children (87 s, SD=43) (P=0.02). There were no significant differences in the duration of action of rocuronium between children without renal failure and in 15 out of 16 children with renal failure. CONCLUSIONS: In children with renal failure, aged over 1 year, a single bolus dose of rocuronium 0.3 mg.kg-1 does not cause a prolonged block, but has a slower onset than in healthy children.

Similar motor block effects and disposition kinetics between lidocaine and (+/-)mepivacaine in patients undergoing axillary brachial plexus block during day case surgery.

The aim of this investigation was to compare the clinical effects and pharmacokinetics of lidocaine (one metabolite) and mepivacaine (two metabolites) in 2 groups of 15 patients undergoing axillary brachial plexus anaesthesia. The study had a randomised design. The 30 patients were divided into 2 groups. The patients received either lidocaine (600 mg = 2.561 mMol + 5 mg ml(-1) adrenaline) or mepivacaine (600 mg = 2.436 mMol + 5 microg ml(-1) adrenaline), injected via the axilla near the brachial plexus over a period of 30 s. Onset of surgical analgesia was defined as the period from the end of the local anaesthetic injection to the loss of pinprick sensation in the distribution of the ulnar, radial, and median nerve. Motor block was measured. Onset of motor block was similar for both drugs. Lidocaine is eliminated biexponentially with a t1/2alpha of 9.95 +/- 14.3 min and a t1/2beta of 2.86 +/- 1.55 h. Lidocaine is metabolised into MEGX (tmax 2.31 +/- 0.84 h; Cmax 0.32 +/- 0.13 mg l(-1); t1/2beta 2.36 +/- 2.35 h; total body clearance was 67.9 +/- 28.9 l h(-1)). Mepivacaine is eliminated rapidly and monoexponentially with a t1/2 of 4.78 +/- 2.38 h, a Cmax of 3.89 +/- 0.83 mg l(-1), and a tmax of 0.41 +/- 0.19 h. The total body clearance of mepivacaine is 50% of that of lidocaine, 26.9 +/- 10.6 l h(-1) vs. 67.9 +/- 28.9 l h-1, respectively (p < 0.0001). (+/-)mepivacaine is metabolised into (+/-)4-OHmepivacaine (Cmax 0.45 +/- 0.25 mg l(-1); t1/2beta 6.48 +/- 6.57 h) and (+/-)2,6-pipecoloxylidide (Cmax 0.56 +/- 0.30 mg l(-1); t1/2beta 1.48 +/- 0.74 h). For the axillary brachial plexus block, lidocaine and mepivacaine show similar pharmacodynamic and pharmacokinetic behaviour, despite the number of metabolites, and can therefore be used to the clinical preference for this regional anaesthetic technique.

The efficacy of radiofrequency lesioning of the cervical spinal dorsal root ganglion in a double blinded randomized study: no difference between 40 degrees C and 67 degrees C treatments.

The efficacy of radiofrequency lesion treatment of the cervical dorsal root ganglion (RF-DRG) in cervicobrachialgia was investigated in 61 patients by a randomized prospective double blinded study. Before lesion treatment the putative pain provoking spinal root was identified by diagnostic blocks with a local anesthetic agent. One group of patients (n = 32, group I) was treated with a radiofrequency lesion of 67 degrees C and in a control group (n = 29, group II) a temperature of 40 degrees C was applied. Three months after treatment a significant reduction in VAS scores was demonstrated in both groups. The outcome of the treatments was identical (VAS reduction: group I, 1.7; group II, 1.9; P = 0.001). In group I a VAS reduction of 3 or more occurred in 11/31 (34%) and in group II in 11/29 (38%) of patients. A VAS reduction of 2 or more occurred in group I in 15/31 (47%) and in group II in 15/29 (51%) of patients. This study suggests that treatment with 40 degrees C radiofrequency application of the dorsal root ganglion is equally effective as treatment at 67 degrees C. Further appraisal of this treatment is required.