[Oral and maxillofacial surgeons' satisfaction of the use of procedural sedation and/or analgesia (PSA) in the clinic]. / Tevredenheid van mka-chirurgen over gebruik procedurele sedatie in de kliniek.

Fear of orofacial interventions is a very common problem. Procedural sedation and/or analgesia (PSA) offers added value in reducing anxiety, pain and discomfort. At the Radboud University Medical Centre (Nijmegen, the Netherlands) PSA is conducted under the guidance of physician assistants, resulting in a high degree of patient satisfaction. In this study, the 115 surgeons' satisfaction with PSA procedures for outpatient orofacial surgical interventions was evaluated by means of questionnaires. The study's conclusion is that oral and maxillofacial surgeons are highly satisfied when PSA is administered to very anxious patients. The collaboration with the department of anaestesiology ensures that the outpatient interventions can be performed safely and efficiently by the oral and maxillofacial surgeon.

[Patient satisfaction with procedural sedation in oral and -maxillofacial surgery]. / Patiënttevredenheid met procedurele sedatie in de mka-chirurgie.

Fear of treatment by an oral and maxillofacial (OMF) surgeon or the dentist is a widespread and deep-rooted phenomenon. A patient can be taught to cope with dental phobia by means of psychological, cognitive behavioural therapy, but in cases of invasive oral treatment, such therapy may be insufficiently effective. For these invasive procedures, sedation serves as an alternative treatment option. The department of Oral and Maxillofacial Surgery at the Radboud University Medical Centre in Nijmegen, the Netherlands, offers the possibility to utilise intravenous sedation with midazolam (Dormicum®) and remifentanil (Ultiva®). This results in a reduction in the experience of axiety and pain, which can lead to an anterograde amnesia for the invasive treatment. Procedural sedation and analgesia (PSA) for OMF surgery demonstrate a high level of patient satisfaction, and therefore offer a good alternative treatment to local and general anaesthesia.

The in vitro mechanisms and in vivo efficacy of intravenous lidocaine on the neuroinflammatory response in acute and chronic pain.

INTRODUCTION: The neuroinflammatory response plays a key role in several pain syndromes. Intravenous (iv) lidocaine is beneficial in acute and chronic pain. This review delineates the current literature concerning in vitro mechanisms and in vivo efficacy of iv lidocaine on the neuroinflammatory response in acute and chronic pain. DATABASES AND DATA TREATMENT: We searched PUBMED and the Cochrane Library for in vitro and in vivo studies from July 1975 to August 2014. In vitro articles providing an explanation for the mechanisms of action of lidocaine on the neuroinflammatory response in pain were included. Animal or clinical studies were included concerning iv lidocaine for acute or chronic pain or during inflammation. RESULTS: Eighty-eight articles regarding iv lidocaine were included: 36 in vitro studies evaluating the effect on ion channels and receptors; 31 animal studies concerning acute and chronic pain and inflammatory models; 21 clinical studies concerning acute and chronic pain. Low-dose lidocaine inhibits in vitro voltage-gated sodium channels, the glycinergic system, some potassium channels and Gαq-coupled protein receptors. Higher lidocaine concentrations block potassium and calcium channels, and NMDA receptors. Animal studies demonstrate lidocaine to have analgesic effects in acute and neuropathic pain syndromes and anti-inflammatory effects early in the inflammatory response. Clinical studies demonstrate lidocaine to have advantage in abdominal surgery and in some neuropathic pain syndromes. CONCLUSIONS: Intravenous lidocaine has analgesic, anti-inflammatory and antihyperalgesic properties mediated by an inhibitory effect on ion channels and receptors. It attenuates the neuroinflammatory response in perioperative pain and chronic neuropathic pain.

Lidocaine increases the anti-inflammatory cytokine IL-10 following mechanical ventilation in healthy mice.

BACKGROUND: Mechanical ventilation (MV) induces an inflammatory response that may result in (acute) lung injury. Lidocaine, an amide local anesthetic, has anti-inflammatory properties in vitro and in vivo, possibly due to an attenuation of pro-inflammatory cytokines, intracellular adhesion molecule-1 (ICAM-1), and reduction of neutrophils influx. We hypothesized an attenuation of MV-induced inflammatory response with intravenously administered lidocaine. METHODS: Lidocaine (Lido) (2, 4, and 8 mg/kg/h) was intravenously administered during 4 h of MV with a tidal volume of 8 ml/kg, positive end expiratory pressure 1,5 cmH2O and FiO2 0.4. We used one ventilated control (CON) group receiving vehicle. After MV, mice were euthanized, and lungs and blood were immediately harvested, and cytokine levels and ICAM-1 levels were measured in plasma and lung homogenates. Pulmonary neutrophils influx was determined in LEDER-stained slices of lungs. Anesthetic need was determined by painful hind paw stimulation. RESULTS: Lidocaine-treated animals (Lido 2, 4 and 8 mg/kg/h) showed higher interleukin (IL)-10 plasma levels compared to control animals. Lidocaine treatment with 8 mg/kg/h (Lido 8) resulted in higher IL-10 in lung homogenates. No differences were observed in pro-inflammatory cytokines, ICAM-1, and pulmonary influx between the different ventilated groups. CONCLUSIONS: Intravenously administered lidocaine increases levels of plasma IL-10 with infusion from 2, 4, and 8 mg/kg/h and pulmonary levels of IL-10 with 8 mg/kg/h in a murine mechanical ventilation model. Intravenously administered lidocaine appears to reduce anesthetic need in mice.

Resveratrol attenuates NF-κB-binding activity but not cytokine production in mechanically ventilated mice.

BACKGROUND: Mechanical ventilation (MV) can result in inflammation and subsequent lung injury. Toll-like receptor (TLR)4 and NF-κB are proposed to play a crucial role in the MV-induced inflammatory response. Resveratrol (RVT) exhibits anti-inflammatory effects in vitro and in vivo supposedly by interfering with TLR4 signaling and NF-κB. In the present study, we investigated the role of RVT in MV-induced inflammation in mice. METHODS: RVT (10 mg/kg, 20 mg/kg and 40 mg/kg) or vehicle was intraperitoneally administered 1 h before start of MV (4 h, tidal volume 8 ml/kg, positive end-expiratory pressure 1,5 cmH2 O and FiO2 0.4). Blood and lungs were harvested for cytokine analysis. DNA binding activity of transcription factor NF-κB was measured in lung homogenates. RESULTS: MV resulted in elevated pulmonary concentrations of IL-1ß, IL-6, keratinocyte-derived chemokine (KC) and NF-κB DNA-binding activity. RVT at 10, 20 and 40 mg/kg reduced NF-κB's DNA-binding activity following MV compared with ventilated controls. However, no differences in cytokine release were found between RVT-treated and control ventilated mice. Similarly, in plasma, MV resulted in elevated concentrations of TNF-α, KC and IL-6, but RVT did not affect cytokine levels. CONCLUSIONS: RVT abrogates the MV-induced increase in pulmonary NF-κB activity but does not attenuate cytokine levels. This implies a less prominent role for NF-κB in MV-induced inflammation than previously assumed.

Polytrauma at the Emergency Department; can we relate arterial blood gas analysis to a shock classification?

OBJECTIVE: Shock is defined as a change of circulation which results in hypoxia at the tissue level. Lactate and base deficit (BD) are associated with a high risk of multiple organ dysfunction in trauma patients. In this study we evaluated the influence of early recognition of shock in trauma patients. METHODS: In a retrospective study, relevant data were collected from the Radboud University Nijmegen Medical Centre (RUNMC) database between January 2009 and December 2010. Vital parameters were taken at the accident scene, and patients were divided into four shock classes. Arterial blood gas analysis was performed on arrival in the emergency department. Statistical analysis was performed with SPSS version 17.0. Statistical significance was assumed at p ≤ 0.05. RESULTS: A total of 255 patients were included. Patients who suffered from prehospital shock, and those who were intubated prior to hospital admittance showed a bad outcome, presenting with a more severe metabolic acidosis, higher ISS and higher mortality. There was a significant difference for bicarbonate and BD between shockclass I + II and shockclass III + IV, respectively 22.7 vs. 19.7 and -3.4 vs. -6.9. Intubated patients had a decreased bicarbonate and BD compared to not intubated patients, respectively 21.81 vs. 23.24 and -5.08 vs. -2.38. Mortality and ISS were higher in patients in shock class III and IV. Significant differences in serum lactate levels were not found. CONCLUSIONS: Prehospital shock influences patient outcome; outcome of patients is related to initial shock classification. Further validation of our shock classification, however, is necessary.

α7 nicotinic acetylcholine receptor agonist GTS-21 attenuates ventilator-induced tumour necrosis factor-α production and lung injury.

BACKGROUND: Mechanical ventilation (MV) induces an inflammatory response that can lead to lung injury. The vagus nerve can limit the inflammatory response through the cholinergic anti-inflammatory pathway. We evaluated the effects of stimulation of the cholinergic anti-inflammatory pathway with the selective partial α7 nicotinic acetylcholine receptor (α7nAChR) agonist GTS-21 on inflammation and lung injury induced by MV using clinically relevant ventilator settings. Furthermore, we investigated whether altering endogenous cholinergic signalling, by administration of the non-specific nAChR antagonist mecamylamine and the peripherally acting acetylcholinesterase inhibitor neostigmine, modulates the MV-induced inflammatory response. METHODS: C57BL6 mice were injected i.p. with either the selective α7nAChR agonist GTS-21 (8 mg kg(-1)), the acetylcholinesterase inhibitor neostigmine (80 µg kg(-1)), the nAChR antagonist mecamylamine (1 mg kg(-1)), or a placebo; followed by 4 h of MV (8 ml kg(-1), 1.5 cm H(2)O PEEP). RESULTS: MV resulted in release of cytokines in plasma and lungs compared with unventilated mice. Lung and plasma levels of tumour necrosis factor (TNF)-α, but not of interleukin-10, were lower in GTS-21-treated animals compared with placebo (P<0.05). In addition, GTS-21 lowered the alveolar-arterial gradient, indicating improved lung function (P=0.04). Neither neostigmine nor mecamylamine had an effect on MV-induced inflammation or lung function. CONCLUSIONS: MV with clinically relevant ventilator settings results in pulmonary and systemic inflammation. Stimulation of the cholinergic anti-inflammatory pathway with GTS-21 attenuates MV-induced release of TNF-α, which was associated with reduced lung injury. Modulation of endogenous cholinergic signalling did not affect the MV-induced inflammatory response. Selective stimulation of the cholinergic anti-inflammatory pathway may represent new treatment options for MV-induced lung injury.

Isoflurane attenuates pulmonary interleukin-1beta and systemic tumor necrosis factor-alpha 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. METHODS: Healthy C57BL6 mice (n=34) were mechanically ventilated (tidal volume, 8 ml/kg; positive end-expiratory pressure, 4 cmH(2)O; and fraction of inspired oxygen, 0.4) for 4 h under general anesthesia using a mix of ketamine, medetomidine and atropine (KMA). Animals were divided into four groups: (1) Unventilated control group; (2) MV group using KMA anesthesia; (3) MV group using KMA with 0.25 MAC isoflurane; (4) MV group using KMA with 0.75 MAC isoflurane. Cytokine levels were measured in lung homogenate and plasma. Leukocytes were counted in lung tissue. RESULTS: Lung homogenates: MV increased pro-inflammatory cytokines. In mice receiving KMA+ isoflurane 0.75 MAC, no significant increase in interleukin (IL)-1beta was found compared with non-ventilated control mice. PLASMA: MV induced a systemic pro-inflammatory response. In mice anesthetized with KMA+ isoflurane (both 0.25 and 0.75 MAC), no significant increase in tumor necrosis factor (TNF)-alpha was found compared with non-ventilated control mice. CONCLUSIONS: The present study is the first to show that isoflurane attenuates the pulmonary IL-1beta and systemic TNF-alpha response following MV in healthy mice.

Cytokines and biotrauma in ventilator-induced lung injury: a critical review of the literature.

BACKGROUND: Mechanical ventilation is known to induce and aggravate lung injury. One of the underlying mechanisms is biotrauma, an inflammatory response in which cytokines play a crucial role. OBJECTIVE: To review the literature on the role of cytokines in ventilator-induced lung injury (VILI) and multiple organ dysfunction syndrome (MODS). MATERIAL AND METHODS: 57 English written, peer-reviewed articles on cytokines in in-vitro settings (n=5), ex-vivo models (n=9) in-vitro models (n=19) and clinical trials (n=24). RESULTS: Mechanical ventilation (MV) can induce cytokine upregulation in both healthy and injured lungs. The underlying mechanisms include alveolar cellular responses to stretch with subsequent decompartimentalisation due to concomitant cellular barrier damage. The cytokines involved are interleukin (IL)-8 and CXC chemokines, and probably IL-6, IL-1beta and tumour necrosis factor (TNF)-alpha. Cytokines are important for signalling between inflammatory cells and recruiting leucocytes to the lung. There is strong circumstantial evidence that the release of cytokines into the systemic circulation contributes to the pathogenesis of MODS. Multiple studies demonstrate the relation between elevated proinflammatory cytokine concentrations and mortality. CONCLUSION: Cytokines are likely to play a role in the various interrelated processes that lead to VILI and other MV-related complications, such as MODS and possibly ventilatorassociated pneumonia. Cytokines are good surrogate endpoints in exploring the pathogenesis and pathophysiology of VILI in both experimental and clinical studies.