Meeting nutritional targets of critically ill patients by combined enteral and parenteral nutrition: review and rationale for the EFFORTcombo trial.

While medical nutrition therapy is an essential part of the care for critically ill patients, uncertainty exists about the right form, dosage, timing and route in relation to the phases of critical illness. As enteral nutrition (EN) is often withheld or interrupted during the intensive care unit (ICU) stay, combined EN and parenteral nutrition (PN) may represent an effective and safe option to achieve energy and protein goals as recommended by international guidelines. We hypothesise that critically ill patients at high nutritional risk may benefit from such a combined approach during their stay on the ICU. Therefore, we aim to test if an early combination of EN and high-protein PN (EN+PN) is effective in reaching energy and protein goals in patients at high nutritional risk, while avoiding overfeeding. This approach will be tested in the here-presented EFFORTcombo trial. Nutritionally high-risk ICU patients will be randomised to either high (≥2·2 g/kg per d) or low protein (≤1·2 g/kg per d). In the high protein group, the patients will receive EN+PN; in the low protein group, patients will be given EN alone. EN will be started in accordance with international guidelines in both groups. Efforts will be made to reach nutrition goals within 48-96 h. The efficacy of the proposed nutritional strategy will be tested as an innovative approach by functional outcomes at ICU and hospital discharge, as well as at a 6-month follow-up.

Deceased organ donation activity and efficiency in Switzerland between 2008 and 2017: achievements and future challenges.

BACKGROUND: Various actions have been taken during the last decade to increase the number of organs from deceased donors available for transplantation in Switzerland. This study provides an overview on key figures of the Swiss deceased organ donation and transplant activity between 2008 and 2017. In addition, it puts the evolution of the Swiss donation program's efficiency in relation to the situation in the neighboring countries. METHODS: This study is an analysis of prospective registry data, covering the period from 1 January 2008 to 31 December 2017. It includes all actual deceased organ donors (ADD) in Switzerland. Donor data were extracted from the Swiss Organ Allocation System. The "donor conversion index" (DCI) methodology and data was used for the comparison of donation program efficiency in Switzerland, Germany, Austria, Italy and France. RESULTS: During the study period there were 1116 ADD in Switzerland. The number of ADD per year increased from 91 in 2008 to 145 in 2017 (+ 59%). The reintroduction of the donation after cardiocirculatory death (DCD) program in 2011 resulted in the growth of annual percentages of DCD donors, reaching a maximum of 27% in 2017. The total number of organs transplanted from ADD was 3763 (3.4 ± 1.5 transplants per donor on average). Of these, 48% were kidneys (n = 1814), 24% livers (n = 903), 12% lungs (n = 445), 9% hearts (n = 352) and 7% pancreata or pancreatic islets (n = 249). The donation program efficiency assessment showed an increase of the Swiss DCI from 1.6% in 2008 to 2.7% in 2017 (+ 69%). The most prominent efficiency growth was observed between 2012 and 2017. Even though Swiss donation efficiency increased during the study period, it remained below the DCI of the French and Austrian donation programs. CONCLUSION: Swiss donation activity and efficiency grew during the last decade. The increased donation efficiency suggests that measures implemented so far were effective. The lower efficiency of the Swiss donation program, compared to the French and Austrian programs, may likely be explained by the lower consent rate in Switzerland. This issue should be addressed in order to achieve the goal of more organs available for transplantation.

Brain metabolism is significantly impaired at blood glucose below 6 mM and brain glucose below 1 mM in patients with severe traumatic brain injury.

INTRODUCTION: The optimal blood glucose target following severe traumatic brain injury (TBI) must be defined. Cerebral microdialysis was used to investigate the influence of arterial blood and brain glucose on cerebral glucose, lactate, pyruvate, glutamate, and calculated indices of downstream metabolism. METHODS: In twenty TBI patients, microdialysis catheters inserted in the edematous frontal lobe were dialyzed at 1 microl/min, collecting samples at 60 minute intervals. Occult metabolic alterations were determined by calculating the lactate- pyruvate (L/P), lactate- glucose (L/Glc), and lactate- glutamate (L/Glu) ratios. RESULTS: Brain glucose was influenced by arterial blood glucose. Elevated L/P and L/Glc were significantly reduced at brain glucose above 1 mM, reaching lowest values at blood and brain glucose levels between 6-9 mM (P < 0.001). Lowest cerebral glutamate was measured at brain glucose 3-5 mM with a significant increase at brain glucose below 3 mM and above 6 mM. While L/Glu was significantly increased at low brain glucose levels, it was significantly decreased at brain glucose above 5 mM (P < 0.001). Insulin administration increased brain glutamate at low brain glucose, but prevented increase in L/Glu. CONCLUSIONS: Arterial blood glucose levels appear to be optimal at 6-9 mM. While low brain glucose levels below 1 mM are detrimental, elevated brain glucose are to be targeted despite increased brain glutamate at brain glucose >5 mM. Pathogenity of elevated glutamate appears to be relativized by L/Glu and suggests to exclude insulin- induced brain injury.

Transcranial color-coded duplex sonography allows to assess cerebral perfusion pressure noninvasively following severe traumatic brain injury.

OBJECTIVE: Assess optimal equation to noninvasively estimate intracranial pressure (eICP) and cerebral perfusion pressure (eCPP) following severe traumatic brain injury (TBI) using transcranial color-coded duplex sonography (TCCDS). DESIGN AND SETTING: This is an observational clinical study in a university hospital. PATIENTS: A total of 45 continuously sedated (BIS < 50), normoventilated (paCO(2) > 35 mmHg), and non-febrile TBI patients. METHODS: eICP and eCPP based on TCCDS-derived flow velocities and arterial blood pressure values using three different equations were compared to actually measured ICP and CPP in severe TBI patients subjected to standard treatment. Optimal equation was assessed by Bland-Altman analysis. RESULTS: The equations: ICP = 10:927 x PI(pulsatility index) - 1:284 and CPP = 89:646 - 8:258 PI resulted in eICP and eCPP similar to actually measured ICP and CPP with eICP 10.6 +/- 4.8 vs. ICP 10.3 +/- 2.8 and eCPP 81.1 +/- 7.9 vs. CPP 80.9 +/- 2.1 mmHg, respectively. The other two equations, eCPP = (MABP x EDV)/mFV + 14 and eCPP = mFV / (mFV - EDV)] x (MABP - RRdiast), resulted in significantly decreased eCPP values: 72.9 +/- 10.1 and 67 +/- 19.5 mmHg, respectively. Superiority of the first equation was confirmed by Bland-Altman revealing a smallest standard deviations for eCPP and eICP. CONCLUSIONS: TCCDS-based equation (ICP = 10.927 x PI - 1.284) allows to screen patients at risk of increased ICP and decreased CPP. However, adequate therapeutic interventions need to be based on continuously determined ICP and CPP values.

Expiratory automatic endotracheal tube compensation reduces dynamic hyperinflation in a physical lung model.

INTRODUCTION: The effect of expiratory endotracheal tube (ETT) resistance on dynamic lung inflation is unknown. We hypothesized that ETT resistance causes dynamic lung hyperinflation by impeding lung emptying. We further hypothesized that compensation for expiratory ETT resistance by automatic tube compensation (ATC) attenuates dynamic lung hyperinflation. METHODS: A ventilator equipped with the original ATC mode and operating in a pressure-targeted mode was connected to a physical lung model that consists of four equally sized glass bottles filled with copper wool. Inspiratory pressure, peak expiratory flow, trapped lung volume and intrinsic positive end-expiratory pressure (PEEP) were assessed at combinations of four inner ETT diameters (7.0, 7.5, 8.0 and 8.5 mm), four respiratory rates (15, 20, 25 and 30/minute), three inspiratory pressures (3.0, 4.5 and 6.0 cmH2O) and four lung compliances (113, 86, 58 and 28 ml/cmH2O). Intrinsic PEEP was measured at the end of an expiratory hold manoeuvre. RESULTS: At a given test lung compliance, inspiratory pressure and ETT size, increasing respiratory rates from 15 to 30/minutes had the following effects: inspiratory tidal volume and peak expiratory flow were decreased by means of 25% (range 0% to 51%) and 11% (8% to 12%), respectively; and trapped lung volume and intrinsic PEEP were increased by means of 25% (0% to 51%) and 26% (5% to 45%), respectively (all P < 0.025). At otherwise identical baseline conditions, introduction of expiratory ATC significantly attenuated (P < 0.025), by approximately 50%, the respiratory rate-dependent decreases in inspiratory tidal volume and the increases in trapped lung volume and intrinsic PEEP. CONCLUSIONS: In a lung model of pressure-targeted ventilation, expiratory ETT resistance caused dynamic lung hyperinflation during increases in respiratory rates, thereby reducing inspiratory tidal volume. Expiratory ATC attenuated these adverse effects.

Long-acting local anesthetics attenuate FMLP-induced acute lung injury in rats.

BACKGROUND: Endothelin-1 (ET-1) is a mediator of lung diseases and a potent pulmonary vasoconstrictor. In addition to thromboxane A2, it participates in the formation of lung edema. Both lidocaine and mepivacaine attenuate the increase of pulmonary arterial pressure (PAP) and lung edema development. We examined the effects of procaine, bupivacaine, and ropivacaine on experimentally evoked PAP increase and ET-1 release. METHODS: PAP and lung weight were measured in isolated rat lungs during perfusion with Krebs-Henseleit hydroxyethyl starch buffer. Bupivacaine, ropivacaine, or procaine was added to the solution at concentrations of 10(-2)-10(-7) mg/kg. ET-1 levels were measured in the perfusate by enzyme-immunoassay, and thromboxane A2 levels were assayed by radioimmunoassay. N-formyl-L-leucine-methionyl-L-phenylalanine was used to activate human polymorphonuclear neutrophils. RESULTS: Bupivacaine, ropivacaine, and procaine significantly attenuated increases of PAP (P < 0.05) and resulted in a reduction of lung weight in these treatment groups compared with the sham group (P < 0.05). The long-acting anesthetics bupivacaine and ropivacaine (P < 0.05), but not procaine, reduced ET-1 levels, produced low inflammation rates, and did not affect lung structures at doses from 10(-3) to 10(-6) mg/kg. CONCLUSION: Bupivacaine and ropivacaine attenuated N-formyl-L-leucine-methionyl-L-phenylalanine-induced PAP, reduced lung edema, and diminished ET-1 release. Lidocaine and mepivacaine are more effective in reducing PAP and edema formation, but long-acting local anesthetics also inhibit ET-1 depletion and therefore have increased anti-inflammatory properties.

Effect of high-dose sodium selenite in cardiac surgery patients: A randomized controlled bi-center trial.

BACKGROUND & AIMS: Cardiac surgery is accompanied by oxidative stress and systemic inflammatory response, which may be associated with organ dysfunction and increased mortality. Selenium and selenoenzymes are important constituents of anti-oxidative defense. We hypothesized that high-dose sodium selenite supplementation can attenuate the postoperative inflammation and might, therefore, improve clinical outcome. METHODS: Randomized, placebo-controlled, double-blinded, bi-center study on 411 adult patients undergoing elective cardiac surgery. Patients received an intravenous bolus of 4000 µg selenium (in the form of sodium selenite) or placebo after induction of anesthesia and 1000 µg/d selenium or placebo during their intensive care unit (ICU) stay. Primary outcome measure was the Sequential Organ Failure Assessment (SOFA) score on the second postoperative day. Secondary endpoints included the change in perioperative selenium levels, change of inflammatory and cardiac markers, use of vasoactive medication, incidence of acute kidney injury, ICU and hospital length of stay, and mortality. RESULTS: The perioperative administration of high-dose sodium selenite prevented the postoperative drop of blood and serum selenium levels, reduced the number of patients depending on postoperative vasoactive support but failed to reduce the postoperative SOFA score and its related organ-specific scores compared to placebo. Except for an increase of postoperative procalcitonin and bilirubin levels in the sodium selenite group, other inflammatory markers, organ function variables and clinical endpoints remained unchanged. CONCLUSIONS: The perioperative administration of high-dose sodium selenite in cardiac surgery patients prevented the postoperative fall of blood selenium levels and reduced the need for postoperative vasoactive support by a yet unknown mechanism. TRIAL REGISTRATION: Registered under ClinicalTrials.gov Identifier no. NCT01141556.

Detection of partial endotracheal tube obstruction by forced pressure oscillations.

Rapid airway occlusions during mechanical ventilation are followed immediately by high-frequency pressure oscillations. To answer the question if the frequency of forced pressure oscillations is an indicator for partial obstruction of the endotracheal tube (ETT) we performed mathematical simulations and studies in a ventilated physical lung model. Model-derived predictions were evaluated in seven healthy volunteers. Partial ETT obstruction was mimicked by decreasing the inner diameter (ID) of the ETT. In the physical model ETTs of different ID were used. In spontaneously breathing volunteers viscous fluid was applied into the ETT's lumen. According to the predictions derived from mathematical simulations, narrowing of the ETT's ID from 9.0 to 7.0mm decreased the frequency of the pressure oscillations by 11% while changes of the respiratory system's compliance had no effect. In volunteers, a similar reduction (10.9%) was found when 5 ml fluid were applied. We conclude that analysis of pressure oscillations after flow interruption offers a tool for non-invasive detection of partial ETT obstruction.

Short-term effects of positive end-expiratory pressure on breathing pattern: an interventional study in adult intensive care patients.

INTRODUCTION: Positive end-expiratory pressure (PEEP) is used in mechanically ventilated patients to increase pulmonary volume and improve gas exchange. However, in clinical practice and with respect to adult, ventilator-dependent patients, little is known about the short-term effects of PEEP on breathing patterns. METHODS: In 30 tracheally intubated, spontaneously breathing patients, we sequentially applied PEEP to the trachea at 0, 5 and 10 cmH2O, and then again at 5 cmH2O for 30 s each, using the automatic tube compensation mode. RESULTS: Increases in PEEP were strongly associated with drops in minute ventilation (P < 0.0001) and respiratory rate (P < 0.0001). For respiratory rate, a 1 cmH2O change in PEEP in either direction resulted in a change in rate of 0.4 breaths/min. The effects were exclusively due to changes in expiratory time. Effects began to manifest during the first breath and became fully established in the second breath for each PEEP level. Identical responses were found when PEEP levels were applied for 10 or 60 s. Post hoc analysis revealed a similar but stronger response in patients with impaired respiratory system compliance. CONCLUSION: In tracheally intubated, spontaneously breathing adult patients, the level of PEEP significantly influences the resting short-term breathing pattern by selectively affecting expiratory time. These findings are best explained by the Hering-Breuer inflation/deflation reflex.

Increased renovascular response to angiotensin II in persons genetically predisposed to arterial hypertension disappears after chronic angiotensin-converting enzyme inhibition.

OBJECTIVE AND METHODS: Functional changes in the kidneys of healthy men with (FH+) (n = 15) and without (FH-) (n = 15) family history of primary arterial hypertension were examined during administration of low-dose exogenous angiotensin II (A2) (1 ng/kg per min) before and after acute (1 mg intravenous enalaprilat) and chronic (7 days oral enalapril, 30 mg/day) angiotensin-converting enzyme (ACE) inhibition. RESULTS: Before chronic ACE inhibition, A2 increased mean arterial blood pressure (FH+, 8.7 +/- 0.8 mmHg; FH-, 8.9 +/- 0.9 mmHg), plasma immunoreactive A2 (FH+, 21 +/- 2 pg/ml; FH-, 18 +/- 3 pg/ml) and plasma aldosterone (FH+, 64 +/- 7 pg/ml; FH-, 56 +/- 6 pg/ml) to a similar degree in both groups. Chronic ACE inhibition had no impact on A2 blood pressure, plasma A2, or plasma aldosterone effects. A2 significantly increased renal vascular resistance in both groups (FH+, 3956 +/- 462 dyne s cm(-5); FH-, 2219 +/- 550 dyne s cm(-5)), but the effect was more pronounced in FH+ (P = 0.02). Glomerular hemodynamics, estimated by a modified Gomez model, revealed increased afferent and efferent responsiveness to A2 in FH+ subjects. These differences disappeared after chronic ACE inhibition when total, afferent and efferent sensitivities to A2 were similar in both groups. CONCLUSIONS: Systemic blood pressure and plasma aldosterone responses to A2 were similar in men with or without a genetic disposition to primary arterial hypertension. However, our data demonstrate that men with a family history of hypertension have increased renovascular sensitivity to A2, and that chronic ACE inhibition normalizes their sensitivity.

Effect of non-hypotensive haemorrhage on plasma catecholamine levels and cardiovascular variability in man.

BACKGROUND: It is well known from animal research that non-hypotensive haemorrhage produces sympathoexcitatory responses assessable by both the rise in plasma catecholamine levels and the shift of autonomic influences on the heart to more sympathetic and less parasympathetic control. Data in humans are restricted. METHODS: Heart rate variability (HRV), systolic blood pressure (FINAPRES) variability (BPV), and catecholamine plasma levels were measured before and after haemorrhage in 30 healthy blood donors and compared with those from 10 control subjects without blood loss. Spectral power of HRV and BPV in very low (0.02-0.06 Hz), low (0.07-0.14 Hz), and high (0.15-0.40 Hz) frequency bands were calculated by Fourier analysis. Catecholamine plasma levels were assayed by dual column reverse-phased high-performance liquid chromatography (HPLC). RESULTS: Haemorrhage of 5.6 +/- 1.2 ml kg-1 body weight increased plasma norepinephrine levels (215 +/- 92 pg ml-1 versus 254 +/- 95 pg ml-1; P = 0.002), increased BPV in the low frequency band (Mayer waves; 1.8 +/- 1.0 ln [mmHg(2)] versus 2.0 +/- 0.9 ln [mmHg(2)]; P = 0.021), and decreased the vagally transmitted high frequency HRV (6.9 +/- 1.1 ln [MI(2)] versus 6.5+/-1.2 ln [MI(2)]; P<0.0001), but did not induce significant changes in heart rate (66 +/- 11 bpm versus 67 +/- 11 bpm; P = 0.79) and arterial blood pressure (mean values: 84 +/- 13 mmHg versus 87 +/- 13 mmHg; P = 0.12). CONCLUSIONS: As suggested by plasma norepinephrine levels, systolic BPV and HRV, non-hypotensive haemorrhage produces sympathoexcitatory responses as well as vagal withdrawal of heart rate control in humans.

Continuous monitoring of tracheal pressure including spot-check of endotracheal tube resistance.

During mechanical ventilation, the resistance of the endotracheal and tracheostomy tube (ETT) highly influences analysis of respiratory system mechanics and imposes additional work of breathing for the spontaneously breathing patient which both can be circumvented by applying the automatic tube compensation (ATC) mode. In the ATC mode, tracheal pressure (ptrach) is continuously calculated on the basis of measured flow and airway pressure using predetermined tube specific coefficients. However, as during long-term ventilation the ETT might become partially obstructed by secretions or tube kinking, the predetermined coefficients are no longer valid rendering calculation of ptrach inaccurate. We propose an easy-to-handle maneuver for the bedside determination of current tube coefficients in the tracheally intubated patient. Based on check-spot measurement of ptrach, current tube coefficients are determined by a least-squares fit procedure valid for the partially obstructed ETT with the indwelling pressure-measuring catheter (PMC). To correct for the removal of the PMC, the relationship between tube coefficients with and those without indwelling PMC has been determined in a laboratory investigation. Accuracy of the procedure was determined during artificial ETT obstruction by comparing calculated with measured ptrach. Correspondence between calculated and measured ptrach has been found excellent. We conclude that by adopting this bedside procedure periodically, accurate calculation of ptrach is guaranteed and the advantages of the ATC mode are ensured even in long-term ventilatory support.

Swiss Monitoring of Potential Organ Donors (SwissPOD): a prospective 12-month cohort study of all adult ICU deaths in Switzerland.

BACKGROUND: The Swiss Monitoring of Potential Organ Donors (SwissPOD) was initiated to investigate the causes of the overall low organ donation rate in Switzerland. The objective of our study was an assessment of the donation after brain death (DBD) process in Swiss adult intensive care units (ICUs), and to provide an overview of the donation efficiency as well as of the reasons for non-donation. METHODS: SwissPOD is a prospective cohort study of all deaths in Swiss ICUs and accident and emergency departments. This study is an analysis of SwissPOD data of all patients who deceased in an adult ICU between 1 September 2011 and 31 August 2012. RESULTS: Out of 3,667 patients who died in one of the 79 adult ICUs participating in SwissPOD, 1,204 were possible, 198 potential, 133 eligible, and 94 utilised DBD donors. The consent rate was 48.0% and the conversion rate 47.5%. In 80.0% of cases, the requests for donation took place before brain death was diagnosed, resulting in a similar proportion of consents and objections as when requests were made after brain death diagnosis. CONCLUSIONS: Despite the low donation rate, Swiss adult ICUs are performing well in terms of the conversion rate, similar to major European countries. The refusal rate is among the highest in Europe, which clearly has a negative impact on the donation rate. Optimising the request process seems to be the most effective means of increasing the donation rate.

SodiUm SeleniTe Adminstration IN Cardiac Surgery (SUSTAIN CSX-trial): study design of an international multicenter randomized double-blinded controlled trial of high dose sodium-selenite administration in high-risk cardiac surgical patients.

BACKGROUND: Cardiac surgery has been shown to result in a significant decrease of the antioxidant selenium, which is associated with the development of multiorgan dysfunction and increased mortality. Thus, a large-scale study is needed to investigate the effect of perioperative selenium supplementation on the occurrence of postoperative organ dysfunction. METHODS/DESIGN: We plan a prospective, randomized double-blind, multicenter controlled trial, which will be conducted in North and South America and in Europe. In this trial we will include 1,400 high-risk patients, who are most likely to benefit from selenium supplementation. This includes patients scheduled for non-emergent combined and/or complex procedures, or with a predicted operative mortality of ≥ 5% according to the EuroSCORE II. Eligible patients will be randomly assigned to either the treatment group (bolus infusion of 2,000 µg sodium selenite immediately prior to surgery, followed by an additional dosage of 2,000 µg at ICU admission, and a further daily supplementation of 1,000 µg up to 10 days or ICU discharge) or to the control group (placebo administration at the same time points).The primary endpoint of this study is a composite of 'persistent organ dysfunction' (POD) and/or death within 30 days from surgery (POD + death). POD is defined as any need for life-sustaining therapies (mechanical ventilation, vasopressor therapy, mechanical circulatory support, continuous renal replacement therapy, or new intermittent hemodialysis) at any time within 30 days from surgery. DISCUSSION: The SUSTAIN-CSX™ study is a multicenter trial to investigate the effect of a perioperative high dosage sodium selenite supplementation in high-risk cardiac surgical patients. TRIAL REGISTRATION: This trial was registered at Clinicaltrials.gov (identifier: NCT02002247) on 28 November 2013.

Severe traumatic brain injury in a high-income country: an epidemiological study.

This adult cohort determined the incidence and patients' short-term outcomes of severe traumatic brain injury (sTBI) in Switzerland and age-related differences. A prospective cohort study with a follow-up at 14 days was performed. Patients ≥16 years of age sustaining sTBI and admitted to 1 of 11 trauma centers were included. sTBI was defined by an Abbreviated Injury Scale of the head (HAIS) score >3. The centers participated from 6 months to 3 years. The results are presented as percentages, medians, and interquartile ranges (IQRs). Subgroup analyses were performed for patients ≤65 years (younger) and >65 (elderly). sTBI was observed in 921 patients (median age, 55 years; IQR, 33-71); 683 (74.2%) were male. Females were older (median age, 67 years; IQR, 42-80) than males (52; IQR, 31-67; p<0.00001). The estimated incidence was 10.58 per 100,000 inhabitants per year. Blunt trauma was observed in 879 patients (95.4%) and multiple trauma in 283 (30.7%). Median Glasgow Coma Score (GCS) on the scene was 9 (IQR 4-14; 8 in younger, 12 in elderly) and in emergency departments 5 (IQR, 3-14; 3 in younger, 8 in elderly). Trauma mechanisms included the following: 484 patients with falls (52.6%; younger, 242 patients [50.0%]; elderly, 242 [50.0%]), 291 with road traffic accidents (31.6%; younger, 237 patients [81.4%]; elderly, 54 [18.6%]), and 146 with others (15.8%). Mortality was 30.2% (24.5% in younger, 40.9% in elderly). Median GCS at 14 days was 15 (IQR, 14-15) without differences among subgroups. Estimated incidence of sTBI in Switzerland was low, age was high, and mortality considerable. The elderly had higher initial GCS and a higher death rate, but high GCS at 14 days.

Estimating intratidal nonlinearity of respiratory system mechanics: a model study using the enhanced gliding-SLICE method.

In the clinical situation and in most research work, the analysis of respiratory system mechanics is limited to the estimation of single-value compliances during static or quasi-static conditions. In contrast, our SLICE method analyses intratidal nonlinearity under the dynamic conditions of mechanical ventilation by calculating compliance and resistance for six conjoined volume portions (slices) of the pressure-volume loop by multiple linear regression analysis. With the gliding-SLICE method we present a new approach to determine continuous intratidal nonlinear compliance. The performance of the gliding-SLICE method was tested both in computer simulations and in a physical model of the lung, both simulating different intratidal compliance profiles. Compared to the original SLICE method, the gliding-SLICE method resulted in smaller errors when calculating the compliance or pressure course (all p < 0.001) and in a significant reduction of the discontinuity error for compliance determination which was reduced from 12.7 +/- 7.2 cmH(2)O s L(-1) to 0.8 +/- 0.3 cmH(2)O s L(-1) (mathematical model) and from 7.2 +/- 3.9 cmH(2)O s L(-1) to 0.4 +/- 0.2 cmH(2)O s L(-1) (physical model) (all p < 0.001). We conclude that the new gliding-SLICE method allows detailed assessment of intratidal nonlinear respiratory system mechanics without discontinuity error.