Transport of the patient with trauma: a narrative review.

Trauma and injury place a significant burden on healthcare systems. In most high-income countries, well-developed acute pre-hospital and trauma care systems have been established. In Europe, mobile physician-staffed medical teams are available for the most severely injured patients and apply a wide variety of lifesaving interventions at the same time as ensuring patient comfort. In trauma systems providing pre-hospital care, medical interventions are performed earlier in the patient journey and do not affect time to definite care. The mode of transport from the accident scene depends on the organisation of the healthcare system and the level of hospital care to which the patient is transported. This varies from 'scoop and run' to a basic community care setting, to advanced helicopter emergency medical service transport to a level 4 trauma centre. Secondary transport of trauma patients to a higher level of care should be avoided and may lead to a delay in definitive care. Critically injured patients must be accompanied by at least two healthcare professionals, one of whom must be skilled in cardiopulmonary resuscitation and advanced airway management techniques. Ideally, the standard of care provided during transport, including the level of monitoring, should mirror hospital care. Pre-hospital care focuses on the critical care patient, but the majority of injured patients need only close observation and pain management during transport. Providing comfort and preventing additional injury is the responsibility of the whole transport team.

[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.

Femoral nerve catheter vs local infiltration for analgesia in fast track total knee arthroplasty: short-term and long-term outcomes.

BACKGROUND: The aim was to compare the effects on short-term and long-term pain and functional outcome of periarticular local anaesthetic infiltration (LIA) with LIA of the posterior knee capsule in combination with a femoral nerve block (FNB) catheter in patients undergoing total knee arthroplasty. METHODS: Eighty patients were randomised to one of two groups: Subjects in group LIA received periarticular LIA with ropivacaine 0.2% for postoperative analgesia; subjects in group FNB received LIA of the posterior capsule and a FNB catheter. The primary outcome parameter was functional capacity of the knee 12 months after surgery. Secondary parameters included mobility as determined by accelerometer data, pain, satisfaction with the analgesic regimen, hospital length of stay, and use of pain medication 3 and 12 months after surgery. RESULTS: There were no differences between groups in long-term functional capacity, patient satisfaction and hospital length of stay. In the first 2 days, subjects in group FNB had slightly lower pain scores and used less opioids, and subjects in group LIA had a higher level of accelerometer activity. Three and 12 months after surgery, subjects in group FNB had lower maximum pain scores and were less likely to use any pain medication 12 months after surgery. CONCLUSIONS: Both techniques were similar regarding long-term functional outcome. Subjects in group FNB had slightly lower pain scores and lower opioid consumption after operation, lower maximum pain scores at 3 and 12 months, and were less likely to use any pain medication at 12 months. CLINICAL TRIAL REGISTRATION: NCT01966263.

Deep neuromuscular blockade improves surgical conditions during low-pressure pneumoperitoneum laparoscopic donor nephrectomy.

BACKGROUND: Evidence indicates that low-pressure pneumoperitoneum (PNP) reduces postoperative pain and analgesic consumption. A lower insufflation pressure may hamper visibility and working space. The aim of the study is to investigate whether deep neuromuscular blockade (NMB) improves surgical conditions during low-pressure PNP. METHODS: This study was a blinded randomized controlled multicenter trial. 34 kidney donors scheduled for laparoscopic donor nephrectomy randomly received low-pressure PNP (6 mmHg) with either deep (PTC 1-5) or moderate NMB (TOF 0-1). In case of insufficient surgical conditions, the insufflation pressure was increased stepwise. Surgical conditions were rated by the Leiden-Surgical Rating Scale (L-SRS) ranging from 1 (extremely poor) to 5 (optimal). RESULTS: Mean surgical conditions were significantly better for patients allocated to a deep NMB (SRS 4.5 versus 4.0; p < 0.01). The final insufflation pressure was 7.7 mmHg in patients with deep NMB as compared to 9.1 mmHg with moderate NMB (p = 0.19). The cumulative opiate consumption during the first 48 h was significantly lower in patients receiving deep NMB, while postoperative pain scores were similar. In four patients allocated to a moderate NMB, a significant intraoperative complication occurred, and in two of these patients a conversion to an open procedure was required. CONCLUSIONS: Our data show that deep NMB facilitates the use of low-pressure PNP during laparoscopic donor nephrectomy by improving the quality of the surgical field. The relatively high incidence of intraoperative complications indicates that the use of low pressure with moderate NMB may compromise safety during LDN. Clinicaltrials.gov identifier: NCT 02602964.

Deep neuromuscular block to optimize surgical space conditions during laparoscopic surgery: a systematic review and meta-analysis.

Neuromuscular block (NMB) is frequently used in abdominal surgery to improve surgical conditions by relaxation of the abdominal wall and prevention of sudden muscle contractions. The evidence supporting routine use of deep NMB is still under debate. We aimed to provide evidence for the superiority of routine use of deep NMB during laparoscopic surgery. We performed a systematic review and meta-analysis of studies comparing the influence of deep vs moderate NMB during laparoscopic procedures on surgical space conditions and clinical outcomes. Trials were identified from Medline, Embase, and Central databases from inception to December 2016. We included randomized trials, crossover studies, and cohort studies. Our search yielded 12 studies on the effect of deep NMB on the surgical space conditions. Deep NMB during laparoscopic surgeries improves the surgical space conditions when compared with moderate NMB, with a mean difference of 0.65 (95% confidence interval (CI): 0.47-0.83) on a scale of 1-5, and it facilitates the use of low-pressure pneumoperitoneum. Furthermore, deep NMB reduces postoperative pain scores in the postanaesthesia care unit, with a mean difference of - 0.52 (95% CI: -0.71 to - 0.32). Deep NMB improves surgical space conditions during laparoscopic surgery and reduces postoperative pain scores in the postanaesthesia care unit. Whether this leads to fewer intraoperative complications, an improved quality of recovery, or both after laparoscopic surgery should be pursued in future studies. The review methodology was specified in advance and registered at Prospero on July 27, 2016, registration number CRD42016042144.

Pharmacokinetics of 400 mg ropivacaine after periarticular local infiltration analgesia for total knee arthroplasty.

BACKGROUND: Although considered safe, no pharmacokinetic data of high dose, high volume local infiltration analgesia (LIA) with ropivacaine without the use of a surgical drain or intra-articular catheter have been described. The purpose of this study is to describe the maximum total and unbound ropivacaine concentrations (Cmax , Cu max ) and corresponding maximum times (Tmax , Tu max ) of a single-shot ropivacaine (200 ml 0.2%) and 0.75 mg epinephrine (1000 µg/ml) when used for LIA in patients for total knee arthroplasty. METHODS: In this prospective cohort study, 20 patients were treated with LIA of the knee for primary total knee arthroplasty. Plasma samples were taken at 20, 40, 60, 90, 120, 240, 360 min and at 24 h after tourniquet release, in which total and unbound ropivacaine concentrations were determined. RESULTS: Results are given as median [IQR]. Highest ropivacaine concentration (Cmax ) was 1.06 µg/ml [0.34]; highest unbound ropivacaine concentration (Cu max ) was 0.09 µg/ml [0.05]. The corresponding time to reach the maximum concentration for total ropivacaine was 312 min [120] after tourniquet release, and for the unbound fraction 265 [110] min after tourniquet release. CONCLUSION: Although great inter-individual variability was found between the maximum ropivacaine concentrations, both maximum total and unbound serum concentrations of ropivacaine remained well below the assumed systemic toxic thresholds of 4.3 and 0.56 µg/ml.

Anti-Müllerian hormone does not predict time to pregnancy: results of a prospective cohort study.

In order to study whether ovarian reserve tests (ORTs) can predict time to ongoing pregnancy, we conducted a prospective cohort study in a cohort of healthy pregnancy planners. A total of 102 pregnancy planners were followed for 1 year, or until ongoing pregnancy occurred, after cessation of contraceptives). A baseline measurement of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH) and antral follicle count (AFC) was conducted. At the end of follow-up, a semen analysis was performed and chlamydia antibody titres were assessed. A univariate prediction model demonstrated age and the AFC to be significantly capable of predicting time to pregnancy (hazard ratio 0.92, 95% CI 0.87-0.98, p = 0.01; 1.04, 95% CI 1.01-1.07, p = 0.02 respectively). In the multivariate model, however, correcting for female age, we found no predictive effect of AMH, basal FSH or the AFC for time to ongoing pregnancy (hazard ratios 1.43, 95% CI 0.84-2.46, p = 0.36; 0.96, 95% CI 0.86-1.06, p = 0.43; 1.03, 95% CI 1.00-1.07, p = 0.08, respectively). This was confirmed by the low C-statistic. We therefore concluded that baseline AMH, AFC or FSH levels do not predict time to ongoing pregnancy in a cohort of healthy pregnancy planners. These results limit the usability of these ORTs in the assessment of current fertility.

Does anti-Müllerian hormone predict menopause in the general population? Results of a prospective ongoing cohort study.

STUDY QUESTION: Do ovarian reserve tests (ORTs) predict age at natural menopause (ANM) in a cohort of healthy women with a regular menstrual cycle? SUMMARY ANSWER: Of the ORTs researched, anti-Müllerian hormone (AMH) alone predicts age at menopause. However, its predictive value decreased with increasing age of the woman, prediction intervals were broad and extreme ages at menopause could not be predicted. WHAT IS KNOWN ALREADY: A fixed interval is hypothesized to exist between ANM and age at loss of natural fertility. Therefore, if it is possible to predict ANM, one could identify women destined for early menopause and thus at higher risk for age-related subfertility. Of ORTs researched in the prediction of ANM, AMH is the most promising one. STUDY DESIGN, STUDY SIZE AND DURATION: A long-term, extended follow-up study was conducted, results of the first follow-up round were previously published. Two hundred and sixty-five normo-ovulatory women (21-46 years) were included between 1992 and 2001, 49 women (18.5%) could not be reached in the current follow-up round. PARTICIPANTS, SETTING, METHODS: Two hundred and sixty-five healthy normo-ovulatory women were included, recruited in an Academic hospital. We measured baseline AMH, follicle-stimulating hormone and the antral follicle count (AFC). At follow-up (2009 and 2013), menopausal status was determined via questionnaires. Cox regression analysis calculated time to menopause (TTM) using age and ORT. A check of (non-) proportionality of the predictive effect of AMH was performed. A Weibull survival model was used in order to predict individual ANM. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 155 women were available for analyses. Eighty-one women (37.5%) had become post-menopausal during follow-up. Univariable Cox regression analysis demonstrated age and ORTs to be significantly correlated with TTM. Multivariable Cox regression analysis, adjusting for baseline age and smoking; however, demonstrated AMH alone to be an independent predictor of TTM (Hazard Ratio 0.70, 95% Confidence Interval 0.56-0.86, P-value <0.001). A (non-)proportionality analysis of AMH over time demonstrated AMH's predictive effect to decline over time. LIMITATIONS, REASON FOR CAUTION: The observed predictive effect of AMH became less strong with increasing age of the woman. Individual AMH-based age at menopause predictions did not cover the full range of menopausal ages, but did reduce the variation around the predicted ANM from 20 to 10.1 years. WIDER IMPLICATIONS OF THE FINDINGS: Age-specific AMH levels are predictive for ANM. Unlike in our previous publication however, a declining AMH effect with increasing age was observed. This declining AMH effect is in line with recent long-term follow-up data published by others. Moreover, the accompanying predictive inaccuracy observed in individual age at menopause predictions based on AMH, makes this marker currently unsuitable for use in clinical practice. STUDY FUNDING/COMPETING INTERESTS: No external funds were used for this study. M.D., M.J.C.E, S.L.B., G.J.S. and I.A.J.R. have nothing to declare. J.S.E.L. has received fees and grant support from the following companies (in alphabetical order): Ferring, Merck-Serono, MSD, Organon, Serono and Schering Plough. F.J.M.B. receives monetary compensation: member of the external advisory board for Merck Serono, the Netherlands; consultancy work for Gedeon Richter, Belgium; educational activities for Ferring BV, the Netherlands; strategic cooperation with Roche on automated AMH assay development.

Correlation of bupivacaine 0.5% dose and conversion from spinal anesthesia to general anesthesia in cesarean sections.

BACKGROUND: Failed spinal anesthesia for cesarean sections may require conversion to general anesthesia. The aim of this study was to determine whether the administered spinal bupivacaine dose for performing a cesarean section under spinal anesthesia was related to the conversion rate to general anesthesia. METHODS: Retrospective analysis was performed on 1252 electronic data and file of patients who underwent a cesarean section under spinal anesthesia between 2004 and 2011. RESULTS: In 15 patients, spinal anesthesia was converted into general anesthesia due to block failure. Patients in whom a bupivacaine dose of 8 mg or smaller was administered had significantly higher conversion rate (3/61 (4.9%) patients and 12/1191 (1.0%) patients, respectively; p < 0.05.). The relative risk of conversion with a 8 mg dose or lower is 4.88 (95% CI 1.41 - 16.85). CONCLUSION: This retrospective study shows that a low dose administration a bupivacaine 0.5% for spinal anesthesia in cesarean section patients elicits significantly more frequent conversion to general anesthesia.

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.

Anti-Mullerian hormone is a more accurate predictor of individual time to menopause than mother's age at menopause.

STUDY QUESTION: In the prediction of time to menopause (TTM), what is the added value of anti-Müllerian hormone (AMH) when mother's age at natural menopause (ANM) is also known? SUMMARY ANSWER: AMH is a more accurate predictor of individual TTM than mother's age at menopause. WHAT IS KNOWN ALREADY: Mother's ANM is considered a proxy for daughter's ANM although studies on its predictive accuracy are non-existent. AMH is a biomarker with a known capacity to predict ANM. However, its added value on top of known predictors, like mother's ANM, is unknown. STUDY DESIGN, SIZE, DURATION: Population-based cohort studies were used. To assess any additive predictive value of mother's ANM, 164 mother-daughter pairs were used (Group 1). To assess the added value of AMH, a second group of 150 women in whom AMH and mother's ANM were recorded prior to a 12-year follow-up period during which daughter's ANM was assessed was used (Group 2). PARTICIPANTS/MATERIALS, SETTING, METHODS: Group 1 consisted of participants of the DOM cohort (an ongoing breast cancer study). Group 2 was a pooled cohort of women with regular menstrual cycles from two independent published studies. Cox proportional hazards analysis estimated uni- and multivariate regression coefficients for female age at study entry, mother's ANM and AMH in the prediction of TTM. Discrimination of models was assessed with C-statistics. Clinical added value of AMH was quantified with a net reclassification index (NRI). MAIN RESULTS AND THE ROLE OF CHANCE: A model with female age and mother's ANM had a c-statistic of 79 and 85% in groups 1 and 2, respectively. Both age and mother's ANM were significantly associated with TTM (HR 1.54 and HR 0.93 for age and mother's ANM in Cohort 1 and HR 1.59 and HR 0.89 in Group 2, respectively. P-value for all <0.001). In Group 2, the multivariate model with age, mother's ANM and AMH had a c-statistic of 92%, and only female age and AMH remained significantly associated with TTM (HR 1.41 P < 0.0001; HR 0.93 P = 0.08 and HR 0.06 P < 0.0001 for age, mother's ANM and AMH, respectively). The mean weighted NRI suggests that a 47% improvement in predictive accuracy is offered by adding AMH to the model of age and mother's ANM. In conclusion, AMH and mother's ANM both have added value in forecasting TTM for the daughter based on her age. In comparison, AMH is a more accurate added predictor of TTM than mother's ANM. LIMITATIONS, REASONS FOR CAUTION: The cohort of women is relatively small and different cohorts of women were pooled. WIDER IMPLICATIONS OF THE FINDINGS: This study shows that AMH is a more accurate predictor of ANM than mother's ANM. However, before achieving clinical applicability, the certainty with which a woman's prediction is made must improve. The association between mother's ANM and TTM in daughters did not appear to be influenced by whether ANM was recorded by mothers or daughters--an important finding because in the clinical setting daughters usually provide this information. STUDY FUNDING/COMPETING INTEREST(S): No funding was received and there were no competing interests in direct relation to this study.

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.

Ultrasound-guided needle handling using a guidance positioning system in a phantom.

The SonixGPS™ needle guidance positioning system provides navigation assistance to facilitate needle handling during ultrasound-guided procedures. Each of 20 inexperienced nurse anaesthetists performed 12 different ultrasound-guided tasks in a porcine phantom. Using both in-plane and out-of-plane approaches, they inserted a needle and made contact with metal rods at depths of 2, 4 and 6 cm. We compared their performances without and with navigation as paired observations. Using the out-of-plane approach, navigation yielded shorter execution times (26 s vs 14 s, respectively; p = 0.01) and fewer needle repositionings (8 vs 3, respectively; p = 0.001). Using the in-plane approach, the needle was more visible with navigation assistance: 24% vs 52% of execution time, respectively (95% CI: 44%-12%; p = 0.0025). Better needle visibility was associated with shorter execution times and fewer needle repositionings. Combining ultrasound-guided techniques with the needle guidance positioning system may reduce tissue manipulation, thus improving patient comfort and safety.

Perioperative Care for Patients with Neuromuscular Disorders in the Netherlands - A Questionnaire Study Among Anaesthesiologists, Neurologists and Clinical Geneticists.

BACKGROUND: Patients with neuromuscular disorders are at increased risk of suffering perioperative complications. Current knowledge concerning this topic is based on small retrospective studies and expert opinion. Therefore, an individualized multidisciplinary approach to perioperative anaesthesia planning is invaluable to anticipate difficulties and to optimize outcomes. OBJECTIVE: To evaluate current practice regarding preoperative counselling and perioperative care of neuromuscular patients, with the aim to facilitate standardization and improvement of perioperative care for neuromuscular patients. METHODS: A questionnaire-based cross-sectional, observational study was conducted between July, 1st 2020 and December, 31st, 2020 in Dutch anaesthesia, neurology and clinical genetics departments. Main outcome measures were 1.) frequency of consultation requests for neuromuscular patients prior to surgery, 2.) current practice, educational activities and departmental approach to this topic and 3.) preoperative counselling of neuromuscular patients. RESULTS: A total of 83 departments participated. Consultations for a neuromuscular patient scheduled for anaesthesia were requested from anaesthesia and neurology department only infrequently. Local guidelines concerning perioperative care of neuromuscular patients were available in 36.4% of the participating departments. Quality of specific training for residents and staff anaesthetists/neurologists covering perioperative care of neuromuscular patients was rated as 'very good' or 'good' by 42.9%. Neuromuscular patients scheduled for surgery were 'always' or 'often' discussed in multidisciplinary meetings involving anaesthesiologists and neurologists in 20.8% of the participating departments. CONCLUSION: Perioperative care for neuromuscular patients in the Netherlands is highly variable and might benefit from guidelines, education of health care professionals and multidisciplinary meetings between anaesthesiologists and neurologists on a regular basis.

Pyruvate: immunonutritional effects on neutrophil intracellular amino or alpha-keto acid profiles and reactive oxygen species production.

For the first time the immunonutritional role of pyruvate on neutrophils (PMN), free α-keto and amino acid profiles, important reactive oxygen species (ROS) produced [superoxide anion (O(2) (-)), hydrogen peroxide (H(2)O(2))] as well as released myeloperoxidase (MPO) acitivity has been investigated. Exogenous pyruvate significantly increased PMN pyruvate, α-ketoglutarate, asparagine, glutamine, aspartate, glutamate, arginine, citrulline, alanine, glycine and serine in a dose as well as duration of exposure dependent manner. Moreover, increases in O(2) (-) formation, H(2)O(2)-generation and MPO acitivity in parallel with intracellular pyruvate changes have also been detected. Regarding the interesting findings presented here we believe, that pyruvate fulfils considerably the criteria for a potent immunonutritional molecule in the regulation of the PMN dynamic α-keto and amino acid pools. Moreover it also plays an important role in parallel modulation of the granulocyte-dependent innate immune regulation. Although further research is necessary to clarify pyruvate's sole therapeutical role in critically ill patients' immunonutrition, the first scientific successes seem to be very promising.

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.