Increased Plasma Levels of Danger-Associated Molecular Patterns Are Associated With Immune Suppression and Postoperative Infections in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Introduction: Danger-associated molecular patterns (DAMPs) can elicit immune responses and may subsequently induce an immune-suppressed state. Previous work showed that increased plasma levels of DAMPs are associated with immune suppression and increased susceptibility toward infections in trauma patients. Like trauma, major surgical procedures, such as cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), are also thought to cause profound DAMP release. Furthermore, the incidence of postoperative infections in these patients, ranging from 10 to 36%, is very high compared to that observed in patients undergoing other major surgical procedures. We hypothesized that the double hit of surgical trauma (CRS) in combination with HIPEC causes excessive DAMP release, which in turn contributes to the development of immune suppression. To investigate this, we assessed DAMP release in patients undergoing CRS-HIPEC, and investigated its relationship with immune suppression and postoperative infections. Methods: In 20 patients undergoing CRS-HIPEC, blood was obtained at five time points: just before surgery (baseline), after CRS, after HIPEC, at ICU admission, and 1 day after surgery. Circulating levels of DAMPs [heat shock protein (HSP)70, high mobility group box (HMGB)1, S100A12, S100A8/S100A9, nuclear (n)DNA, mitochondrial (mt)DNA, lactate dehydrogenase (LDH), a marker of unscheduled cell death], and cytokines [tumor necrosis factor (TNF)α, IL-6, IL-8, IL-10, macrophage inflammatory protein (MIP)-1α, MIP-1ß, and MCP-1] were measured. The extent of immune suppression was determined by measuring HLA-DR gene expression and ex vivo leukocytic cytokine production capacity. Results: Plasma levels of DAMPs (maximum fold increases of HSP70: 2.1 [1.5-2.8], HMGB1: 5.9 [3.2-9.8], S100A8/S100A9: 3.6 [1.8-5.6], S100A12: 2.6 [1.8-4.3], nDNA 3.9 [1.0-10.8], LDH 1.7 [1.2-2.5]), and all measured cytokines increased profoundly following CRS-HIPEC. Evidence of immune suppression was already apparent during the procedure, illustrated by a decrease of HLA-DR expression compared with baseline (0.5-fold [0.3-0.9]) and diminished ex vivo pro-inflammatory cytokine production capacity. The increase in HMGB1 levels correlated with the decrease in HLA-DR expression (r = -0.46, p = 0.04), and peak HMGB1 concentrations were significantly higher in the five patients who went on to develop a postoperative infection (p = 0.04). Conclusion: CRS-HIPEC is associated with profound DAMP release and immune suppression, and plasma HMGB1 levels are related with the occurrence of postoperative infections in these patients.

Quality of Recovery After Low-Pressure Laparoscopic Donor Nephrectomy Facilitated by Deep Neuromuscular Blockade: A Randomized Controlled Study.

BACKGROUND: The use of low intra-abdominal pressure (<10 mmHg) reduces postoperative pain scores after laparoscopic surgery. OBJECTIVE: To investigate whether low-pressure pneumoperitoneum with deep neuromuscular blockade improves the quality of recovery after laparoscopic donor nephrectomy (LDN). DESIGN, SETTING AND PARTICIPANTS: In a single-center randomized controlled trial, 64 live kidney donors were randomly assigned to 6 or 12 mmHg insufflation pressure. A deep neuromuscular block was used in both groups. Surgical conditions were rated by the five-point Leiden-surgical rating scale (L-SRS), ranging from 5 (optimal) to 1 (extremely poor) conditions. If the L-SRS was insufficient, the pressure was increased stepwise. MAIN OUTCOME MEASURE: The primary outcome measure was the overall score on the quality of recovery-40 (QOR-40) questionnaire at postoperative day 1. RESULTS: The difference in the QOR-40 scores on day 1 between the low- and standard-pressure group was not significant (p = .06). Also the overall pain scores and analgesic consumption did not differ. Eight procedures (24%), initially started with low pressure, were converted to a standard pressure (≥10 mmHg). A L-SRS score of 5 was significantly more prevalent in the standard pressure as compared to the low-pressure group at 30 min after insufflation (p < .01). CONCLUSIONS: Low-pressure pneumoperitoneum facilitated by deep neuromuscular blockade during LDN does not reduce postoperative pain scores nor improve the quality of recovery in the early postoperative phase. The question whether the use of deep neuromuscular blockade during laparoscopic surgery reduces postoperative pain scores independent of the intra-abdominal pressure should be pursued in future studies. TRIAL REGISTRATION: The trial was registered at clinicaltrial.gov before the start of the trial (NCT02146417).

Clinical application of perioperative multimodal analgesia.

PURPOSE OF REVIEW: The experience of intense postoperative pain remains a significant problem in perioperative medicine. The mainstay of postoperative analgetic therapy is the combination of nonopioid agents (e.g. paracetamol and NSAIDs) with strong opioids (e.g. morphine) according to the WHO analgesic ladder. But as the incidence and intensity of postoperative pain remains high, the search for and evaluation of additional concepts is ongoing. This review highlights the current trends of perioperative multimodal analgesia concepts. RECENT FINDINGS: Gabapentinoids, ketamine, dexamethasone and magnesium are effective parts of a multimodal analgesia concept without absolute contraindications and nearly without major negative side effects. Recent publications further define the role of these substances for perioperative use in terms of optimal dosing, positive side effects, relative potency and interaction. SUMMARY: Components of well tolerated and simple advanced multimodal analgesia concepts in the perioperative period are now easy to apply and ready to become a standard in the daily clinical practice.

Is gait speed improving performance of the EuroSCORE II for prediction of early mortality and major morbidity in the elderly?

BACKGROUND: The aim of this study was to verify if gait speed can be an incremental predictor for mortality and/or major morbidity in combination with EuroSCORE II. METHODS: A single center prospective study cohort of 150 patients aged 70 years or older and undergoing cardiac surgery between August 2012 and April 2013. Slow gait speed was defined as a time taken to walk 5 meters of ≥6 second. The logistic EuroSCORE and EuroSCORE II were used for risk stratification. RESULTS: The studied group had a mean age of 77.7±5.2 years and mean gait speed was 4.9±1.01 (3.0-8.6) seconds. Slow gait speed was recorded in 21 patients (14%), indicated as frail, the other 129 patients (86%) as active. The logistic EuroSCORE risk (P=0.528), was not significantly different between the two groups. The EuroSCORE II risk, however, was significantly higher (P=0.023) for the frail group. There was no mortality and no statistically significant difference in percentage of major morbidity between the frail (28.6%) versus 17.1% for the active group (P=0.209) and slow gait speed could not be identified as independent predictor. Nevertheless frailty demonstrated an incremental value to improve performance of the logistic EuroSCORE model to predict early mortality and/or major morbidity in this elderly patient population. This was not so for EuroSCORE II. CONCLUSIONS: We confirm the incremental value of frailty, evaluated by gait speed, to improve mortality and morbidity prediction of the logistic EuroSCORE model in elderly undergoing cardiac surgery. We could not confirm this for the new EuroSCORE II model.

Comparison of the effectiveness of low pressure pneumoperitoneum with profound muscle relaxation during laparoscopic donor nephrectomy to optimize the quality of recovery during the early post-operative phase: study protocol for a randomized controlled clinical trial.

BACKGROUND: Since technique modifications of laparoscopic donor nephrectomy, e.g. retroperitoneoscopic donor nephrectomy or hand-assistance, have not shown significant benefit regarding safety or improvement of recovery, further research should focus on improving postoperative recovery. The use of low pressure pneumoperitoneum has shown to significantly reduce postoperative pain after laparoscopy. To facilitate the use of low pressure pneumoperitoneum, deep neuromuscular block will be used. METHODS/DESIGN: This trial is a phase IV, single center, double-blind, randomized controlled clinical trial in which 64 patients will be randomized to: low pressure pneumoperitoneum (6 mmHg) and deep neuromuscular block or normal pressure pneumoperitoneum (12 mmHg) and deep neuromuscular block. Deep neuromuscular block is defined as post tetanic count < 5. Primary outcome measurement will be Quality of Recovery-40 questionnaire (overall score) on day 1. DISCUSSION: This study is the first randomized study to assess the combination of low pressure pneumoperitoneum in combination with deep neuromuscular block from a patients' perspective. The study findings may also be applicable for other laparoscopic procedures. TRIAL REGISTRATION: The trial was registered at trials.gov (NCT02146417) in July 2014.

Multidisciplinary teamwork improves use of the operating room: a multicenter study.

BACKGROUND: Poor inter-professional collaboration might negatively influence adequate planning of operative procedures. Interventions capable of improving inter-professional collaboration will positively impact professional practice and health care outcomes. Radboud University Medical Center (UMC) redesigned their operating room (OR) scheduling method by implementing cross-functional teams (CFTs). In this center, positive effects of CFTs were already demonstrated in a mono-center study. This study aims to confirm these effects by comparing the Radboud data with data from 6 other similar centers using a nationwide OR benchmark collaborative. STUDY DESIGN: The effect of CFTs was measured by the performance indicator "raw utilization." The Kruskal-Wallis one-way ANOVA was applied to compare OR performance among all 7 centers. The Wilcoxon-Mann-Whitney test was used to determine differences in OR performance between Radboud UMC and the control group. RESULTS: Operating room performance differed significantly among all 7 centers (p<0.0005). Radboud UMC demonstrated the highest median raw utilization of 94% vs 85% in the control group (p<0.0005). Box-and-whisker plots validated the reduced variation during the years, indicating an organizational learning effect. Therefore, not only a better performance than the control group, but also a gradual improvement of this performance during the years. CONCLUSIONS: This study shows that multidisciplinary collaboration in CFTs during the perioperative phase has a positive influence on OR scheduling and use of OR time. Other national databases considering mortality rates also support the idea that introducing CFTs is not only an important condition for improving OR performance, but also for improving quality of care.

Towards a novel monitor of intraoperative awareness: selecting paradigm settings for a movement-based brain-computer interface.

During 0.1-0.2% of operations with general anesthesia, patients become aware during surgery. Unfortunately, pharmacologically paralyzed patients cannot seek attention by moving. Their attempted movements may however induce detectable EEG changes over the motor cortex. Here, methods from the area of movement-based brain-computer interfacing are proposed as a novel direction in anesthesia monitoring. Optimal settings for development of such a paradigm are studied to allow for a clinically feasible system. A classifier was trained on recorded EEG data of ten healthy non-anesthetized participants executing 3-second movement tasks. Extensive analysis was performed on this data to obtain an optimal EEG channel set and optimal features for use in a movement detection paradigm. EEG during movement could be distinguished from EEG during non-movement with very high accuracy. After a short calibration session, an average classification rate of 92% was obtained using nine EEG channels over the motor cortex, combined movement and post-movement signals, a frequency resolution of 4 Hz and a frequency range of 8-24 Hz. Using Monte Carlo simulation and a simple decision making paradigm, this translated into a probability of 99% of true positive movement detection within the first two and a half minutes after movement onset. A very low mean false positive rate of <0.01% was obtained. The current results corroborate the feasibility of detecting movement-related EEG signals, bearing in mind the clinical demands for use during surgery. Based on these results further clinical testing can be initiated.

Diannexin protects against renal ischemia reperfusion injury and targets phosphatidylserines in ischemic tissue.

Renal ischemia/reperfusion injury (IRI) frequently complicates shock, renal transplantation and cardiac and aortic surgery, and has prognostic significance. The translocation of phosphatidylserines to cell surfaces is an important pro-inflammatory signal for cell-stress after IRI. We hypothesized that shielding of exposed phosphatidylserines by the annexin A5 (ANXA5) homodimer Diannexin protects against renal IRI. Protective effects of Diannexin on the kidney were studied in a mouse model of mild renal IRI. Diannexin treatment before renal IRI decreased proximal tubule damage and leukocyte influx, decreased transcription and expression of renal injury markers Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 and improved renal function. A mouse model of ischemic hind limb exercise was used to assess Diannexin biodistribution and targeting. When comparing its biodistribution and elimination to ANXA5, Diannexin was found to have a distinct distribution pattern and longer blood half-life. Diannexin targeted specifically to the ischemic muscle and its affinity exceeded that of ANXA5. Targeting of both proteins was inhibited by pre-treatment with unlabeled ANXA5, suggesting that Diannexin targets specifically to ischemic tissues via phosphatidylserine-binding. This study emphasizes the importance of phosphatidylserine translocation in the pathophysiology of IRI. We show for the first time that Diannexin protects against renal IRI, making it a promising therapeutic tool to prevent IRI in a clinical setting. Our results indicate that Diannexin is a potential new imaging agent for the study of phosphatidylserine-exposing organs in vivo.

Minimum effective volume of local anesthetic for shoulder analgesia by ultrasound-guided block at root C7 with assessment of pulmonary function.

BACKGROUND AND OBJECTIVES: This study was performed to determine the minimum effective volume of ropivacaine 0.75% required to produce effective shoulder analgesia for an ultrasound (US)-guided block at the C7 root level with assessment of pulmonary function. METHODS: Using the Dixon and Massey up-and-down method study design, 20 patients scheduled for elective open shoulder surgery under combined general anesthesia and continuous interscalene brachial plexus block were included. Initial volume of ropivacaine 0.75% was 6 mL; block success or failure determined a 1-mL decrease or increase for the subsequent patient, respectively. General anesthesia was standardized. A continuous infusion of ropivacaine 0.2% was started at a rate of 6 mL/hr at 2 hrs after completion of surgery. Ventilatory function was assessed using spirometry, and movement of the hemidiaphragm was assessed by US. RESULTS: The minimum effective volume of local anesthetic in 50% and 95% of the patients was 2.9 mL (95% confidence interval, 2.4-3.5 mL) and 3.6 mL (95% confidence interval, 3.3-6.2 mL), respectively. Ventilatory function and hemidiaphragmatic movement was not reduced up to and including 2 hrs after completion of surgery, but 22 hrs after start of the continuous infusion of ropivacaine 0.2%, ventilatory function and hemidiaphragmatic movement were significantly reduced (P < 0.001). CONCLUSIONS: The minimum effective volume of local anesthetic for shoulder analgesia for a US-guided block at the C7 root level in 50% and 95% of the patients was 2.9 and 3.6 mL, respectively. Pulmonary function was unchanged until 2 hrs after completion surgery, but reduced 22 hrs after start of a continuous infusion of ropivacaine 0.2%.

Ultrasound-guided continuous phrenic nerve block for persistent hiccups.

BACKGROUND: Phrenic nerve block can be performed and repeated if necessary for persistent hiccups, when conservative and pharmacological treatment is unsuccessful. We report the first description of an in-plane ultrasound (US)-guided phrenic nerve block (PhNB) with a catheter, after US investigation of the bilateral diaphragm, to treat hiccups while avoiding repeated PhNBs. CASE: A 36-year-old man had persistent postoperative hiccups not responding to conservative and pharmacological treatment. Bilateral diaphragmatic US evaluation showed abnormal right-sided movement. A right-sided in-plane US-guided PhNB with catheter was performed. Injection of local anesthetic stopped the hiccups, and a continuous infusion of local anesthetic was started for 24 hrs. After discontinuation of the infusion, the hiccups recurred. Restart of the continuous infusion of the local anesthetic through the catheter was performed, and after discontinuation 24 hrs later, no further hiccups occurred. No adverse effect occurred. CONCLUSIONS: An US-guided in-plane PhNB with catheter is feasible and avoids repeated PhNB when hiccups reoccur. Ultrasound investigation of the bilateral diaphragm should be performed before performing the nerve block.

In-plane ultrasound-guided thoracic paravertebral block: a preliminary report of 36 cases with radiologic confirmation of catheter position.

BACKGROUND AND OBJECTIVES: Thoracic paravertebral block (TPVB) can be used for unilateral surgical procedures. Modifications of the classic approach have been proposed to minimize the risk of pleural puncture. In this study, we evaluated the feasibility and success rate of a transverse in-plane ultrasound (US)-guided TPVB with radiologic confirmation of catheter position. METHODS: A total of 36 patients scheduled for unilateral surgery with a TPVB catheter were included in this prospective study. Ultrasonographically, the transverse process of the thoracic vertebra and rib were identified at the appropriate thoracic level. The transducer was moved cranially until an intercostal US view was obtained, indicated by visualization of the parietal pleura. An in-plane needle insertion approach from lateral to medial was used, and a total of 20 mL ropivacaine 0.75% was injected through the needle and a subsequently threaded catheter, while the spread of local anesthetic was observed. Sensory spread of the block was evaluated by loss of cold sensation in the dermatomes. Catheter position was radiologically evaluated with radiopaque dye. RESULTS: Block success rate was 100%. In all patients, correct radiologic thoracic paravertebral catheter position was confirmed; 1 patient also showed additional epidural spread. The median number of total dermatomal segments with loss of cold sensation was 6. No pneumothorax or contralateral loss of cold sensation occurred. CONCLUSION: An in-plane transverse US-guided TPVB using the described technique is feasible and has a high success rate. In all patients, correct catheter position in the thoracic paravertebral space was radiologically confirmed.

Advanced medical life support procedures in vitally compromised children by a helicopter emergency medical service.

BACKGROUND: To determine the advanced life support procedures provided by an Emergency Medical Service (EMS) and a Helicopter Emergency Medical Service (HEMS) for vitally compromised children. Incidence and success rate of several procedures were studied, with a distinction made between procedures restricted to the HEMS-physician and procedures for which the HEMS is more experienced than the EMS. METHODS: Prospective study of a consecutive group of children examined and treated by the HEMS of the eastern region of the Netherlands. Data regarding type of emergency, physiological parameters, NACA scores, treatment, and 24-hour survival were collected and subsequently analysed. RESULTS: Of the 558 children examined and treated by the HEMS on scene, 79% had a NACA score of IV-VII. 65% of the children had one or more advanced life support procedures restricted to the HEMS and 78% of the children had one or more procedures for which the HEMS is more experienced than the EMS. The HEMS intubated 38% of all children, and 23% of the children intubated and ventilated by the EMS needed emergency correction because of potentially lethal complications. The HEMS provided the greater part of intraosseous access, as the EMS paramedics almost exclusively reserved this procedure for children in cardiopulmonary resuscitation. The EMS provided pain management only to children older than four years of age, but a larger group was in need of analgesia upon arrival of the HEMS, and was subsequently treated by the HEMS. CONCLUSIONS: The Helicopter Emergency Medical Service of the eastern region of the Netherlands brings essential medical expertise in the field not provided by the emergency medical service. The Emergency Medical Service does not provide a significant quantity of procedures obviously needed by the paediatric patient.

A single recruitment maneuver in ventilated critically ill children can translocate pulmonary cytokines into the circulation.

INTRODUCTION: Recruitment maneuvers (RMs) are advocated to prevent pulmonary collapse during low tidal volume ventilation and improve oxygenation. However, convincing clinical evidence for improved outcome is lacking. Recent experimental studies demonstrate that RMs translocate pulmonary inflammatory mediators into the circulation. To determine whether a single RM in ventilated children affects pulmonary and systemic cytokine levels, we performed a prospective intervention study. METHODS: Cardiorespiratory stable ventilated patients (0.5-45 months, n = 7) with acute lung injury were subjected to an RM determining opening and closing pressures (peak inspiratory pressure < or =45 cmH(2)O, positive end expiratory pressure (PEEP) < or =30 cmH(2)O). Before and after RM, cardiorespiratory parameters and ventilator settings were recorded, blood gas analysis performed, and bronchoalveolar lavage fluid and plasma TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10 concentrations were determined. RESULTS: Fifteen minutes after the RM, an increase was observed in plasma tumor necrosis factor-alpha (400% +/- 390% of baseline, P = .04), IL-6 (120% +/- 35%, P = .08), and IL-1beta (520% +/- 535%, P = .04), which decreased at T = 60 minutes, hence indicative of translocation. Recruitment maneuver did not change the plasma levels of the anti-inflammatory IL-10 (105% +/- 12%, P = .5). Apart from a nonsignificant increase of IL-8 after 360 minutes (415% +/- 590%,P = .1), bronchoalveolar cytokine levels were not influenced by the RM. No increase in oxygenation or improvement of lung kinetics was observed. CONCLUSIONS: A single RM can translocate pro-inflammatory cytokines from the alveolar space into the systemic circulation in ventilated critically ill children.

Correlation between ultrasound imaging, cross-sectional anatomy, and histology of the brachial plexus: a review.

The anatomy of the brachial plexus is complex. To facilitate the understanding of the ultrasound appearance of the brachial plexus, we present a review of important anatomic considerations. A detailed correlation of reconstructed, cross-sectional gross anatomy and histology with ultrasound sonoanatomy is provided.

The impact of compliant surfaces on in-hospital chest compressions: effects of common mattresses and a backboard.

PURPOSE: To evaluate, in a hospital setting, the influence of different, common mattresses, with and without a backboard, on chest movement during CPR. DESIGN AND SETTING: Sixty CPR sessions (140s each, 30:2, C:R ratio 1:1) were performed using a manikin on standard hospital mattresses, with or without a backboard in combination with variable weights. Sternum-to-spine compression distance was controlled (range 30-60mm) allowing evaluation of the underlying compliant surface on total hand travel. RESULTS: Movement of the caregiver's hands was significantly larger (up to 111mm at 50mm compression depth, p<0.0001) when sternum-to-spine compressions were performed without a backboard than with one. The extent of this variable extra travel effect depended on the type of mattress as well as the force of compression. Foam mattresses and air chamber systems act as springs and follow hand movement, while 'slow foam' mattresses incorporate time delays, making depth and force sensing harder. A backboard decreases the extra hand movement due to mattress effects by more than 50%, strongly reducing caregiver work. CONCLUSIONS: Total vertical hand movement is significantly, and clinically relevantly much, larger than sternum-to-spine compression depth when CPR is performed on a mattress. Additional movement depends on the type of mattress and can be strongly reduced, but not eliminated, when a backboard is applied. The additional motion and increased work load adds extra complexity to in-hospital CPR. We propose that this should be taken into account during training by in-hospital caregivers.

Hypercapnic acidosis attenuates the pulmonary innate immune response in ventilated healthy mice.

BACKGROUND: Mechanical ventilation with small tidal volumes reduces the development of ventilator-induced lung injury and mortality, but may increase PaCO2. It is not clear whether the beneficial effect of a lung-protective strategy results from reduced ventilation pressures/tidal volumes or is mediated by the effects of hypercapnic acidosis on the inflammatory response involved in the pathogenesis of ventilator-induced lung injury. OBJECTIVE: To analyze whether hypercapnic acidosis affects lung tissue cytokine levels and leukocyte influx in healthy ventilated mice. STUDY DESIGN: Analysis of lung tissue and plasma concentrations of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-6, IL-10, and keratocyte-derived chemokine after 2 hrs of mechanical ventilation (V(t) 8 mL/kg, positive end-expiratory pressure 4 cm H2O) with 0.06% CO2 (room air), 2% CO2, or 4% CO2. SUBJECTS: Healthy C57BL6 mice (n = 40). MEASUREMENTS/RESULTS: PaCO2 and pH were within normal range when ventilated with 0.06% CO2 and significantly changed with 2% and 4% CO2: (mean +/- SD) pH 7.23 +/- 0.06 and 7.15 +/- 0.04, PaCO2 7.9 +/- 1.4 and 10.8 +/- 0.7 kPa, respectively (p < 0.005). Blood pressure remained within normal limits in all animals. Quantitative microscopic analysis showed a 4.7 +/- 3.7-fold increase (p < 0.01) in pulmonary leukocyte influx in normocapnic ventilated animals and a significant reduction in leukocyte influx of 57 +/- 32% (p < 0.01) and 67 +/- 22% (p < 0.01) when ventilated with 2% and 4% CO2, respectively. Normocapnic ventilation induced a significant elevation of lung tissue IL-1beta (1516 +/- 119 ng/mL), TNF-alpha (344 +/- 88 ng/mL), IL-6 (6310 +/- 807 ng/mL), IL-10 (995 +/- 152 ng/mL), and keratocyte-derived chemokine (36,966 +/- 15,294 ng/mL) (all p-values <0.01). Hypercapnic acidosis with 2% respectively 4% CO2 significantly attenuated this increase with 25 +/- 32% and 54 +/- 32% (IL-1beta, p < 0.01); 17 +/- 36% and 58 +/- 33% (TNF-alpha, p < 0.02); 22 +/- 34% and 89 +/- 6% (IL-6, p < 0.01); 20 +/- 31% and 67 +/- 17% (IL-10, p < 0.01) and 16 +/- 44% and 45 +/- 30% (keratocyte-derived chemokine, p = 0.07). CONCLUSION: Hypercapnic acidosis attenuates the mechanical ventilation-induced immune response independent from reduced tidal volumes/pressures and may protect the lung from ventilator induced lung injury.

Continuous positive airway pressure breathing increases cranial spread of sensory blockade after cervicothoracic epidural injection of lidocaine.

BACKGROUND: Continuous positive airway pressure (CPAP) increases the caudad spread of sensory blockade after low-thoracic epidural injection of lidocaine. We hypothesized that CPAP would increase cephalad spread of blockade after cervicothoracic epidural injection. METHODS: Twenty patients with an epidural catheter at the C6-7 or C7-T1 interspace received an epidural dose of lidocaine while breathing at ambient pressure (control group), or while breathing with 7.5 cm H2O CPAP. After injection, we evaluated the spread of sensory blockade. Spirometry variables before and after epidural injection were also measured. RESULTS: Data are presented as median (interquartile range) values. Sensory block ranged from C7 (C4-7) to T4 (T4-6) in the control group and from C2 (C2-4) to T4 (T2-5) in the CPAP group (P = 0.003 for the cranial border). The total number of segments blocked was 7.5 (6.8-9.8) in the control group and 10 (8-12) in the CPAP group (P = 0.13). The number of segments blocked cranial to the injection site was one (0.8-3.5) in the control group and five (3.5-7) in the CPAP group (P = 0.006). The number of patients with a maximal cranial block (up to C2) was one in the control group and seven in the CPAP group (P = 0.02). In both groups, there was a small but significant decrease from baseline in spirometry values, with no differences between groups. CONCLUSION: Applying CPAP during cervicothoracic epidural injection of lidocaine resulted in a more cranial extension of sensory blockade when compared with breathing at ambient pressure.

The Donders model of the circulation in normo- and pathophysiology.

The solution of some recent as well as of long standing problems, unanswerable due to experimental inaccessibility or moral objections are addressed. In this report, a model of the closed human cardiovascular loop is developed. This model, using one set of 88 equations, allows variations from normal resting conditions to exercise, as well as to the ultimate condition of a circulation following cardiac arrest. The principal purpose of the model is to evaluate the continuum of physiological conditions to cardiopulmonary resuscitation (CPR) effects within the circulation.Within the model, Harvey's view of the circulation has been broadened to include impedance-defined flow as a unifying concept, and as a mechanism in CPR. The model shows that depth of respiration, sympathetic stimulation of cardiac contractile properties and baroreceptor activity can exert powerful influences on the increase in cardiac output, while heart and respiratory rate increases tend to exert an inhibiting influence, with the pressure and flow curves compatible with accepted references. Impedance-defined flow encompasses both positive and negative effects.The model also demonstrates the limitations to cardiopulmonary resuscitation caused by external force applied to intrathoracic structures, with effective cardiac output being limited by collapse and sloshing. Stroke volumes from 6 to 51 ml are demonstrated. It shows that the clinical inclination to apply high pressures to intrathoracic structures may not be rewarded with improved net flow.

A comparison of epidural pressures and incidence of true subatmospheric epidural pressure between the mid-thoracic and low-thoracic epidural space.

BACKGROUND: Differences in epidural pressure (EP) may influence the spread of blockade in thoracic epidural anesthesia. We evaluated if EP and the incidence of subatmospheric EP differ between the mid- and low-thoracic epidural space. METHODS: Patients received an epidural catheter at the T3-5 (MID group, n = 20) or T7-10 (LOW group, n = 20) intervertebral space, respectively. The epidural space was identified using a Tuohy needle connected to a pressure transducer, after which EP was measured. RESULTS: The epidural space could not be identified in three patients who were excluded from the study. EP data are presented as median value (interquartile range). Median EP was 1 mm Hg (-1 to 4.5) in the MID group, and 4 mm Hg (2-7.8) in the LOW group (P = 0.04). The incidence of an EP