J. van Egmond

Pre-treatment with capsaicin in a rat osteoarthritis model reduces the symptoms of pain and bone damage induced by monosodium iodoacetate.

A rat model of osteoarthritis was used to investigate the effect of pre-treatment with capsaicin on the symptoms of osteoarthritis induced by the injection of monosodium iodoacetate. This model mimics both histopathology and symptoms associated of human osteoarthritis. Injection of monosodium iodoacetate, an inhibitor of glycolysis, into the femorotibial joints of rodents promotes loss of articular trabecular bone and invokes pain symptoms similar to those noted in human osteoarthritis. Twenty rats were divided in two groups either receiving placebo or monosodium iodoacetate. Each group was subdivided in two groups either receiving pre-treatment with capsaicin two weeks before monosodium iodoacetate injection or not, resulting in four groups of five rats each. The impact of a single intra-articular administration of capsaicin (0.5%) on the generation of evoked mechanical pain (hind limb weight bearing, automated von Frey monofilament and RotaRod tests) and bone lesions (micro-CT scan radiographic analyses of bone structure) following monosodium iodoacetate-induced osteoarthritis in rats was determined. Evoked mechanical pain as monitored over a period of 4 weeks after monosodium iodoacetate injection was abolished in capsaicin pre-treated animals and pain values are comparable to those of capsaicin controls. Chronic joint pathological changes such as bone erosion and trabecular damage were significantly reduced by pre-treatment with a single administration of capsaicin. Decrease of bone volume was considerably ameliorated and trabecular connectivity was substantially better in capsaicin pre-treated animals. Capsaicin, an agonist activator of the vanilloid nociceptors (TRPV1), appears to be effective in protecting bone from arthritic damage. The present results support the hypothesis that capsaicin-sensitive sensory neurons contribute to bone lesions in the monosodium iodoacetate-induced osteoarthritis rat model.

Continuous femoral nerve block after total knee arthroplasty

Background: A continuous femoral nerve block is frequently used as an adjunct therapy after total knee arthroplasty (TKA). However, there is still debate on its benefits.

Experimental neuropathy increases limbic forebrain CRF.

Neuropathic pain is often accompanied by stress, anxiety and depression. Although there is evidence for involvement of corticotropin‐releasing factor (CRF), the detailed neuronal basis of these pain‐related mood alterations is unknown. This study shows that peripheral mononeuropathy was accompanied by changes in limbic forebrain CRF, but did not lead to changes in the functioning of the hypothalamo‐pituitary–adrenal axis and the midbrain Edinger–Westphal centrally projecting (EWcp) neuron population, which play main roles in the organisms response to acute pain. Twenty‐four days after chronic constriction injury (CCI) of the rat sciatic nerve, the oval bed nucleus of the stria terminalis (BSTov) contained substantially more Crf mRNA as did the central amygdala (CeA), which, in addition, possessed more CRF. In contrast, Crf mRNA and CRF contents of the hypothalamic paraventricular nucleus (PVN) were unaffected by CCI. Similarly, EWcp neurons, producing the CRF family member urocortin 1 (Ucn1) and constitutively activated by various stressors including acute pain, did not show an effect of CCI on Ucn1 mRNA or Ucn1. Also, the immediate early gene products cFos and deltaFosB in the EWcp were unaffected by CCI. These results indicate that neuropathic pain does not act via the HPA‐axis or the EWcp, but includes a main role of Crf in the limbic system, which is in clear contrast to stressors like acute and chronic pain, which primarily act on the PVN and the EWcp.

Train-of-four ratio recovery often precedes twitch recovery when neuromuscular block is reversed by sugammadex

Background: Sugammadex reverses rocuronium‐induced neuromuscular block (NMB). In all published studies investigating sugammadex, the primary outcome parameter was a train‐of‐four (TOF) ratio of 0.9. The recovery time of T1 was not described. This retrospective investigation describes the recovery of T1 vs. TOF ratio after the reversal of NMB with sugammadex.

A new approach to anesthesia management in myasthenia gravis: reversal of neuromuscular blockade by sugammadex

A neuromuscular blocking drug (NMBD) induced neuromuscular blockade (NMB) in patients with myasthenia gravis usually dissipates either spontaneously or by administration of neostigmine. We administered sugammadex to a patient with myasthenia gravis to reverse a rocuronium-induced profound NMB. NMBDs predispose such patients to severe postoperative residual paralysis and respiratory complications. Sugammadex binds steroidal NMBDs and, therefore reverses a rocuronium or vecuronium-induced NMB, without interfering with cholinergic transmission. A rapid and complete recovery from profound NMB was achieved and no adverse events were observed. This case suggests that sugammadex is a safe and effective antagonist of a rocuronium induced NMB blockade in patients with myasthenia gravis.

A needle guidance device compared to free hand technique in an ultrasound-guided interventional task using a phantom.

In this in vitro study, a needle guidance device and a ‘free hand’ technique for ultrasound guided needle insertion were compared in a simulated ultrasound‐guided interventional task using a porcine phantom. Residents inexperienced in using ultrasonography were asked to insert a needle, using an in‐plane techniques, and to make contact with metal rods at a depth of 2 and 4 cm in the phantom. The transducer made angles of 90°, 60° and 45° with the surface of the phantom. The times to perform the procedures were significantly shorter and the needle visualisation was significantly better when using the needle guidance device. The residents ranked their satisfaction with the needle‐guidance device significantly better than the ‘free‐hand’ technique. This device may be beneficial when performing ultrasound guided peripheral nerve blocks, especially by inexperienced operators.

Sugammadex in patients with myasthenia gravis.

Unterbuchner and colleagues [1] described in their case report the successful reversal of a rocuronium-induced neuromuscular block in a patient with myasthenia gravis. The authors suggest that more evidence is required to examine the use of sugammadex in patients with myasthenia gravis. We would like to report our experience with two patients (with mild generalised muscle weakness, class IIa in myasthenia gravis severity classification system by Osserman and Jenkins [2] and on chronic cholinesterase inhibitor medication) in which we reversed an intense rocuronium-induced neuromuscular block with sugammadex. Both patients were scheduled for short procedures and subsequently gave consent for publication. After inducing neuromuscular block with rocuronium (0.15 mg.kg, which is 25% of the standard dose required for tracheal intubation in normal patients), both patients developed an intense neuromuscular block [3]. At the end of the surgical procedure, monitoring of the neuromuscular function (TOF-Watch SX; MSD ⁄ Shering-Plough Ireland Ltd, Dublin, Ireland) showed no response of the train-of-four and a post-tetanic count was 0. We then reversed the block with 4.0 mg.kg sugammadex. The time from the administration of sugammadex to 90% recovery of the train-of-four ratio was 162 s for the first patient and 135 s for the second. No adverse changes were observed in arterial blood pressure, heart rate or ECG after the administration of sugammadex. The recovery of anaesthesia was uneventful and no signs of residual neuromuscular block or recurarisation were observed. Although there is controversy whether cholinesterase inhibitor medication should be continued until the time of the operation, if patients are reliant on their cholinesterase inhibitor medication it should probably be continued peri-operatively [4]. As sugammadex does not interfere with cholinergic homeostatic regulation, continuation of cholinesterase inhibitors pre-operatively does not affect the efficacy of the reversal of neuromuscular block by sugammadex and therefore optimal muscle function is preserved. Reversal of a rocuronium-induced neuromuscular block by sugammadex will eliminate the risk of residual neuromuscular blockade in these patients with their highly increased sensitivity to nondepolarizing neuromuscular blocking drugs. The combination of rocuronium and sugammadex may avoid the requirement for suxamethonium. Moreover, the use of sugammadex prevents the need for postoperative mechanical ventilation, often the consequence of using non-depolarizing neuromuscular blocking drugs. Reversal of rocuronium-induced intense neuromuscular block by sugammadex in our two patients with myasthenia gravis was rapid, efficient, and without signs of postoperative residual neuromuscular block. We emphasise that in these two patients reversal of the neuromuscular block was initiated at a level of intense neuromuscular block, in contrast to the case described by Unterbuchner and colleagues. These additional cases contribute additional evidence that the combination of rocuronium and sugammadex for neuromuscular block and its reversal is safe and beneficial in myasthenia gravis.

Electromyographic assessment of blink and corneal reflexes during midazolam administration: useful methods for assessing depth of anesthesia?

Background: There are at least three components of the anesthetic state: loss of consciousness, amnesia and obtundation of reflex responses to noxious stimuli. To investigate the third component, we used a standard electrical stimulus to evoke a blink reflex, which was electromyographically recorded. These data may give information on the anesthetic state.

Isoflurane attenuates pulmonary interleukin‐1β and systemic tumor necrosis factor‐α following mechanical ventilation in healthy mice

Background: Mechanical ventilation (MV) induces an inflammatory response in healthy lungs. The resulting pro‐inflammatory state is a risk factor for ventilator‐induced lung injury and peripheral organ dysfunction. Isoflurane is known to have protective immunological effects on different organ systems. We tested the hypothesis that the MV‐induced inflammatory response in healthy lungs is reduced by isoflurane.

Contractures in skeletal muscle of malignant hyperthermia susceptible patients after in vitro exposure to sevoflurane

Background: Sevoflurane, a potent inhalational anaesthetic agent that is structurally similar to halothane, has some favourable characteristics, but may also be able to trigger malignant hyperthermia (MH) in susceptible patients. The diagnosis of malignant hyperthermia susceptibility relies on the in vitro contracture test on skeletal muscle. The present study was undertaken to investigate whether exposure to sevoflurane of muscles of malignant hyperthermia susceptible (MHS) patients would also cause an abnormal contracture.