Benefits of an individualized perioperative plan for children with autism spectrum disorder.

BACKGROUND: Perioperative care for children with autism spectrum disorder may be challenging. Previous investigators recommend development of an individualized perioperative management plan with caregiver involvement. AIM: The primary goal was to determine the usefulness of an individualized plan based on the decision to provide preoperative sedation stratified by autism spectrum severity level. Secondary goals were to assess the effectiveness of the plan based on subjective assessment of patient behavior at induction of anesthesia and caregiver satisfaction. METHODS: We developed an individualized plan for each child with autism spectrum disorder scheduled for anesthesia. Children were categorized by autism spectrum disorder severity level. With institutional ethics approval, we conducted a retrospective chart review to document need for preoperative sedation, sedation stratified by autism spectrum disorder severity level, behavior at induction, and caregiver satisfaction. RESULTS: Between 2012 and 2014, we successfully prepared a plan for 246 (98%) of 251 surgical or diagnostic procedures in 224 patients. Severity level was distributed as 45% Severity Level 1 and Asperger's, 25% Severity Level 2, and 30% Severity Level 3. The majority (90%) of cases were scheduled as day surgery. Preoperative sedation increased with increasing severity level: Severity Level 1 (21%) or Asperger's (31%), Severity Level 2 (44%), and Severity Level 3 (56%). The odds ratio for sedation use was 5.5 [CI: 2.6-11.5, P<.001] with Severity Level 3 vs Severity Level 1 patients. Cooperation at induction of anesthesia was 90% overall with preoperative sedation administered to 94 (38%) of the entire cohort. Cooperation was greatest in Severity Level 1 (98%) and Asperger's patients (93%) and somewhat less (85%) in patients in Severity Levels 2 and 3. The plan was helpful to guide sedation choices as cooperation did not differ between sedated and unsedated children at any severity level (overall χ2 =2.87 P=.09). Satisfaction among caregivers contacted was 98%. CONCLUSION: The results suggest that an individualized plan is helpful in the perioperative management of children with autism spectrum disorder and that knowledge of autism spectrum disorder severity level may be helpful in determining the need for preoperative sedation.

Pulse pressure variability during hemorrhage and reinfusion in piglets: effects of age and tidal volume.

PURPOSE: The dynamic change in arterial pulse pressure during mechanical ventilation (PPV) predicts fluid responsiveness in adults but may not be applicable to pediatric patients. We compared PPV during hemorrhage and reinfusion in immature vs mature piglets at two clinically relevant tidal volumes (VT). METHODS: Following Institutional Animal Care Committee approval, we measured hemodynamics and PPV in two groups of piglets, 10-15 kg (immature, n = 9) and 25-30 kg (mature, n = 10), under stable intravenous anesthesia at VT = 8 and 10 mL·kg(-1). Measurements were taken at baseline, with blood withdrawal in 5 mL·kg(-1) steps up to 30 mL·kg(-1), and during stepwise reinfusion. For each age group and VT, we constructed receiver operating characteristic (ROC) curves to determine the threshold value that was predictive of fluid responsiveness. RESULTS: Pulse pressure variability was significantly lower in immature vs mature pigs and at VT 8 vs VT 10 at every measurement period. The difference in PPV induced by changing VT was less in immature animals. Significant areas under the ROC curve were obtained in immature pigs at both VTs but in mature animals at VT 10 alone. A PPV threshold was calculated to be 8.2% at VT 8 and 10.9% at VT 10 in immature animals vs 15.9% at VT 10 in mature animals, but sensitivity and specificity were only 0.7. CONCLUSION: Pulse pressure variability values are lower and less sensitive to VT in immature vs mature pigs. Adult PPV thresholds do not apply to pediatric patients, and a single PPV value representing fluid responsiveness should not be assumed.

Cerebral oxygen desaturation during one-lung ventilation: correlation with hemodynamic variables.

PURPOSE: Cerebral desaturation occurs frequently in patients undergoing one-lung ventilation for thoracic surgery. The mechanism of this desaturation is unclear regarding its etiology. The objective of this study was to investigate whether or not decreases in cerebral oxygen saturation associated with one-lung ventilation were a consequence of decreased cardiac output. METHODS: A blinded observational study was conducted in 23 patients undergoing one-lung ventilation with thoracic surgery. Eighteen patients completed the study. Cerebral oxygen saturation was monitored using near-infrared spectroscopy (FORE-SIGHT(®) monitor). Invasive blood pressure was monitored and hemodynamic variables were interrogated using the FloTrac(®) system. Anesthesia was maintained with sevoflurane with a F(i)O(2) of 1.0. Post-hoc analysis involved a comparison between baseline and integrated changes in cerebral saturation, heart rate, stroke index, cardiac index, and stroke volume variability. RESULTS: All patients showed cerebral desaturation from a baseline of two-lung ventilation in the lateral decubitus position following institution of one-lung ventilation. The cardiac index was stable at these times, but with one-lung ventilation, the heart rate decreased and the stroke index increased to maintain a stable product. The integral of heart rate × time was inversely correlated with the integral of cerebral desaturation × time (linear regression analysis; P = 0.02; (df) = 16)). CONCLUSIONS: Cerebral oxygen desaturation was universal during one-lung ventilation in this study. There was no correlation between cerebral desaturation and cardiac output or other hemodynamic variables.

Resolution of pulmonary edema with variable mechanical ventilation in a porcine model of acute lung injury.

OBJECTIVE: Resolution of the acute respiratory distress syndrome (ARDS) requires clearance of pulmonary edema. Biologically variable ventilation (BVV) strategies that improve gas exchange, lung mechanics, and inflammatory mediators in ARDS may be beneficial in this regard. We used quantitative computed tomography (CT), a single indicator thermodilution system (PiCCO®) to determine extravascular lung water (EVLW), and the change in edema protein concentration over time to compare edema clearance with BVV vs conventional mechanical ventilation (CMV) in a porcine ARDS model. METHODS: Sixteen pigs with oleic acid lung injury were randomized to four hours of ventilation with either CMV (n = 8) or BVV (n = 8) at identical low tidal volume and minute ventilation over time. Hemodynamic variables, gas exchange, lung mechanics, and PiCCO derived EVLW were determined hourly. Computed tomography images and edema fluid samples were obtained at baseline lung injury and after four hours of ventilation. Wet and dry lung weights were determined postmortem. RESULTS: At four hours with BVV, peak airway pressure was decreased significantly and lung compliance improved compared with CMV (P = 0.003; P < 0.001, respectively). Hemodynamic variables and gas exchange were not different between groups. Also at four hours, computed tomography revealed an increase in total gas volume (P = 0.001) and a decrease in total lung weight and global lung density (P = 0.005; P = 0.04 respectively) with BVV. These findings were associated with a significant increase in the gas volume of normally aerated lung regions (P < 0.001) and a decrease in the poorly and non-aerated lung regions (P = 0.001). No change in any CT parameter occurred with CMV. The lung weights derived from computed tomography correlated well with postmortem wet weights (R(2) = 0.79; P < 0.01). The decrease in PiCCO derived EVLW from injury to four hours did not differ significantly between BVV and CMV. Extravascular lung water showed no correlation with postmortem wet weights and significantly underestimated lung water. Average alveolar fluid clearance rates were positive (1.4%·hr(-1) (3%)) with BVV and negative with CMV (-2.0%·hr(-1) (4%)). CONCLUSIONS: In a comparison between BVV and CMV, computed tomography evidence suggests that BVV facilitates enhanced clearance and/or redistribution of edema fluid with improved recruitment of atelectatic and poorly aerated lung regions; no such evidence was seen with either single thermodilution measurement of EVLW or edema clearance rates. The results of computed tomography provide further evidence of the benefit of BVV over conventional ventilation in ARDS.

Quantitative computed tomography in porcine lung injury with variable versus conventional ventilation: recruitment and surfactant replacement.

OBJECTIVES: Biologically variable ventilation improves lung function in acute respiratory distress models. If enhanced recruitment is responsible for these results, then biologically variable ventilation might promote distribution of exogenous surfactant to nonaerated areas. Our objectives were to confirm model predictions of enhanced recruitment with biologically variable ventilation using computed tomography and to determine whether surfactant replacement with biologically variable ventilation provides additional benefit in a porcine oleic acid injury model. DESIGN: Prospective, randomized, controlled experimental animal investigation. SETTING: University research laboratory. SUBJECTS: Domestic pigs. INTERVENTIONS: Standardized oleic acid lung injury in pigs randomized to conventional mechanical ventilation or biologically variable ventilation with or without green dye labeled surfactant replacement. MEASUREMENTS AND MAIN RESULTS: Computed tomography-derived total and regional masses and volumes were determined at injury and after 4 hrs of ventilation at the same average low tidal volume and minute ventilation. Hemodynamics, gas exchange, and lung mechanics were determined hourly. Surfactant distribution was determined in postmortem cut lung sections. Biologically variable ventilation alone resulted in 7% recruitment of nonaerated regions (p < .03) and 15% recruitment of nonaerated and poorly aerated regions combined (p < .04). Total and normally aerated regional volumes increased significantly with biologically variable ventilation, biologically variable ventilation with surfactant replacement, and conventional mechanical ventilation with surfactant replacement, while poorly and nonaerated regions decreased after 4 hrs of ventilation with biologically variable ventilation alone (p < .01). Biologically variable ventilation showed the greatest improvement (p < .003, biologically variable ventilation vs. all other groups). Hyperaerated regional gas volume increased significantly with biologically variable ventilation, biologically variable ventilation with surfactant replacement, and conventional mechanical ventilation with surfactant replacement. Biologically variable ventilation was associated with restoration of respiratory compliance to preinjury levels and significantly greater improvements in gas exchange at lower peak airway pressures compared to all other groups. Paradoxically, gas exchange and lung mechanics were impaired to a greater extent initially with biologically variable ventilation with surfactant replacement. Peak airway pressure was greater in surfactant-treated animals with either ventilation mode. Surfactant was distributed to the more caudal/injured lung sections with biologically variable ventilation. CONCLUSIONS: Quantitative computed tomography analysis confirms lung recruitment with biologically variable ventilation in a porcine oleic acid injury model. Surfactant replacement with biologically variable ventilation provided no additional recruitment benefit and may in fact be harmful.

Lactate flux during carotid endarterectomy under general anesthesia: correlation with various point-of-care monitors.

PURPOSE: The ability to assess the brain-at-risk during carotid endarterectomy (CEA) under general anesthesia remains a major clinical problem. Point-of-care monitoring can potentially dictate changes to management intraoperatively. In this observational study, we examined the correlation between a series of point-of-care monitors and lactate flux during CEA. METHODS: Both neurosurgeons and vascular surgeons participated in the study. The patients underwent arterial-jugular venous blood sampling for oxygen, carbon dioxide, glucose, and lactate, n = 26; bispectral index (BIS) monitoring ipsilateral to side of surgery, n = 26; raw and processed electroencephalogram (EEG), n = 22; and bi-frontal cerebral oximetry using the Fore-Sight monitor, n = 20. RESULTS: One patient experienced a new neurological deficit when assessed at 24 hr following surgery. Lactate flux into the brain was correlated with the greatest decrease in cerebral oximetry with carotid cross-clamping; lactate efflux was correlated with the least. The most noticeable changes in processed EEG (density spectral analysis) were also seen with lactate influx, but at a slower time resolution than cerebral oximetry. Loss of autoregulatory behaviour was demonstrated with lactate influx; however, no correlation was seen between lactate flux and BIS monitoring. CONCLUSION: There was a correlation between cerebral oximetry and lactate flux during carotid cross-clamping. The Fore-Sight monitor may be of value as a point-of-care monitor during CEA under general anesthesia. A novel finding of this study is lactate flux into the brain in the presence of a large difference in cerebral oxygenation during cross-clamping of the carotid artery. Registered at clinicaltrials.gov: NCT000737334.

Obstetrical and neonatal outcomes in obese parturients.

OBJECTIVE: Obstetrical risk is increased with maternal obesity. This prospective study was designed to simultaneously evaluate the outcomes in obese parturients and their newborns. METHODS: Patients with a body mass index (BMI) > or =35 were prospectively identified and compared to an equal number of normal weight parturients. Maternal and neonatal outcome measures were compared for the peripartum and neonatal period. RESULTS: We identified 580 obese parturients over a 6 month period and compared them to an equal number of normal weight parturients. The incidence of obesity in this population was 23%. Obesity was associated with increased rates of hypertension, diabetes, and cesarean section. Obese patients were more likely to develop postpartum complications. Neonatal outcomes were compared for infants > or =37 weeks gestation excluding multiple births (496 neonates in the obese group and 520 in the control group). The neonates of obese parturients were more likely to be macrosomic, have 1-minute Apgar scores of < or =7.0 and require admission to a special care unit. Sub-group analysis showed that negative outcomes for parturients and their neonates correlated with increasing BMI. Neonates born to obese diabetic parturients had the highest risk of poor outcomes. CONCLUSIONS: Maternal obesity confers increased risks for both the parturient and their newborn.

A comparison of the ability of the EEGo and BIS monitors to assess emergence following neurosurgery.

PURPOSE: Deep anesthesia during microvascular decompression (MVD) for trigeminal neuralgia and cerebral aneurysm clipping may delay emergence. A new electroencephalographic (EEG) monitor, the EEGo, processes a raw EEG signal using time-delay analysis to display a reproducible signal transition from deep anesthesia through the excitement state to the awake state. We hypothesized that the EEGo monitor would be superior to the bispectral (BIS) monitor, not only in aiding emergence but also in detecting sudden changes in levels of hypnosis. METHODS: Twenty-one patients undergoing neurosurgery were studied (16 MVD, 5 cerebral aneurysm clipping). Each patient had both EEGo and BIS monitoring with only one monitor available for viewing by the anesthesiologist. The anesthetic was titrated based on the available monitor, and the time to emergence was measured. Intraoperative detection of arousal and the timing of burst suppression during propofol administration were also examined. RESULTS: In the MVD patients, there was no statistical difference in wake-up times between the EEGo and BIS groups. Additionally, there were no episodes of intraoperative awareness and no differences in patient satisfaction. Compared to EEGo waveform output, a decrease in BIS output was delayed in four patients receiving propofol for burst suppression during cerebral aneurysm clipping, indicating enhanced hypnosis. One case of intraoperative arousal, which occurred at a BIS reading of 43 arbitrary BIS units, was detected earlier with the EEGo. CONCLUSIONS: While the EEGo was faster than the BIS at indicating planned changes in levels of hypnosis throughout propofol administration prior to temporary clipping during aneurysm surgery, the EEGo was not superior to the BIS monitor in facilitating a more rapid emergence following neurosurgery.

Physiological noise versus white noise to drive a variable ventilator in a porcine model of lung injury.

PURPOSE: Variable ventilation is superior to control mode ventilation in a number of circumstances. The nature of the breathing file used to deliver the variable rate and tidal volume has not been formally examined. METHODS: We compared two different noise files in a randomized prospective trial of variable ventilation. Pigs were anesthetized, intubated, and mechanically ventilated. Oleic acid was infused to introduce lung injury. The animals were ventilated at a tidal volume of 7 mL x kg(-1), in variable mode, with either physiologically-derived noise (variability file - 1,587 breath intervals-obtained from a spontaneously breathing volunteer; n = 10) or a variability file of identical length derived from computer- generated white noise (n = 10). RESULTS: The physiologically-derived noise had a power law alpha-exponent of -0.27 and a Hölder exponent of -0.38, indicative of auto-correlated noise. The computer-generated noise had an alpha-exponent of -0.52 and a Hölder exponent of -0.49, indicative of white noise. Both files showed multifractal characteristics. There were no differences between groups, at any time period, for PaO2, PaCO2, and static or dynamic respiratory system compliance. No differences were observed between groups for wet:dry lung weight ratios or for interleukin-8 in bronchoalveolar lavage fluid. CONCLUSION: This study demonstrates that the nature of the variability files, chosen to drive the variable ventilator, had no effect on indices of gas exchange or respiratory mechanics in this model. A considerable overlap of the multifractal files existed. The potential to drive a variable ventilator using algorithm-derived files with multifractal characteristics, thereby eliminating the requirement to use physiologically-derived signals, is discussed.

Biologically variable ventilation improves gas exchange and respiratory mechanics in a model of severe bronchospasm.

OBJECTIVE: Mechanical ventilation can be lifesaving for status asthmaticus, but how best to accomplish mechanical ventilation is unclear. Biologically variable ventilation (mechanical ventilation that emulates healthy variation) and conventional control mode ventilation (monotonously regular) were compared in an animal model of bronchospasm to determine which approach yields better gas exchange and respiratory mechanics. DESIGN: A randomized prospective trial of biologically variable ventilation vs. control mode ventilation in swine. SETTING: University research laboratory. SUBJECTS: Eighteen farm-raised pigs. INTERVENTIONS: Methacholine was administered as a nebulized aerosol to initiate bronchospasm, defined as doubling of peak inspiratory pressure and respiratory system resistance, and then randomized (n = 9 each group) to either continue control mode ventilation or switch to biologically variable ventilation at the same minute ventilation. Over the next 4 hrs, hemodynamics, blood gases, respiratory mechanics, and carbon dioxide expirograms were recorded hourly. At end-experiment, tracheobronchial lavage was undertaken to determine interleukin-6 and -10 concentrations. MEASUREMENTS AND MAIN RESULTS: Measurements of physiologic variables and inflammatory cytokines showed that biologically variable ventilation significantly improved gas exchange, with greater arterial oxygen tensions (p = .006; group x time interaction), lower arterial carbon dioxide tensions (p = .0003; group effect), lower peak inspiratory pressures (p = .0001; group x time), greater static compliance (p = .0001; group x time), greater dynamic compliance (p = .0001; group x time), and lower total respiratory system resistance (p = .028; group x time), compared with conventional ventilation. The appearance of inflammatory cytokines in bronchoalveolar lavage fluid (interleukin-6 and -10) was not affected by mode of ventilation. CONCLUSIONS: In this experimental model, biologically variable ventilation was superior to control mode ventilation in terms of gas exchange and respiratory mechanics during severe bronchospasm.

Biologically variable bypass reduces enzymuria after deep hypothermic circulatory arrest.

BACKGROUND: Renal injury is common after open-heart surgery. Cardiopulmonary bypass contributes to the problem. We compared conventional nonpulsatile perfusion (NP) to biologically variable perfusion (BVP), which uses a computer controller to restore physiological beat-to-beat variability to roller pump flow. We hypothesized BVP would decrease renal injury after deep hypothermic circulatory arrest. METHODS: Pigs were randomly assigned to either BVP (n = 9) or NP (n = 9), cooled, arrested at 18 degrees C (1 hour), reperfused, and rewarmed and maintained normothermic (3 hours). Additional pigs had NP for a similar time as above, but without circulatory arrest (n = 3), or were sham-treated without bypass (n = 3). Hemodynamics, acid-base status, temperature, and urine volumes were measured. Urinary enzyme markers of tubular injury were compared post-hoc for gamma glutamyl transpeptidase, alkaline phosphatase, and glutathione S-transferase and by urine proteomics using mass spectrometry. RESULTS: Urine output at 1 hour after arrest was 250 +/- 129 mL with BVP versus 114 +/- 66 mL with NP (p < 0.02). All three renal enzyme markers were higher with NP after arrest compared with BVP. In animals on bypass without arrest or those sham-treated, no elevations were seen in renal enzymes. Urine proteomics revealed abnormal proteins, persisting longer with NP. Biologically variable perfusion decreased cooling to 21.0 +/- 9.0 minutes versus 31.7 +/- 7.5 minutes (p < 0.002), and decreased rewarming to 22.1 +/- 3.9 minutes versus 31.2 +/- 5.1 minutes (p < 0.002). CONCLUSIONS: Biologically variable perfusion improved urine output, decreased enzymuria, and attenuated mass spectrometry urine protein signal with more rapid temperature changes. This strategy could potentially shorten bypass duration and may decrease renal tubular injury with deep hypothermic circulatory arrest.

Biologically variable ventilation improves oxygenation and respiratory mechanics during one-lung ventilation.

BACKGROUND: Hypoxemia is common during one-lung ventilation (OLV). Atelectasis contributes to the problem. Biologically variable ventilation (BVV), using microprocessors to reinstitute physiologic variability to respiratory rate and tidal volume, has been shown to be advantageous over conventional monotonous control mode ventilation (CMV) in improving oxygenation during the period of lung reinflation after OLV in an experimental model. Here, using a porcine model, the authors compared BVV with CMV during OLV to assess gas exchange and respiratory mechanics. METHODS: Eight pigs (25-30 kg) were studied in each of two groups. After induction of anesthesia-tidal volume 12 ml/kg with CMV and surgical intervention-tidal volume was reduced to 9 ml/kg. OLV was initiated with an endobronchial blocker, and the animals were randomly allocated to either continue CMV or switch to BVV for 90 min. After OLV, a recruitment maneuver was undertaken, and both lungs were ventilated for a further 60 min. At predetermined intervals, hemodynamics, respiratory gases (arterial, venous, and end-tidal samples) and mechanics (airway pressures, static and dynamic compliances) were measured. Derived indices (pulmonary vascular resistance, shunt fraction, and dead space ventilation) were calculated. RESULTS: By 15 min of OLV, arterial oxygen tension was greater in the BVV group (group x time interaction, P = 0.003), and shunt fraction was lower with BVV from 30 to 90 min (group effect, P = 0.0004). From 60 to 90 min, arterial carbon dioxide tension was lower with BVV (group x time interaction, P = 0.0001) and dead space ventilation was less from 60 to 90 min (group x time interaction, P = 0.0001). Static compliance was greater by 60 min of BVV and remained greater during return to ventilation of both lungs (group effect, P = 0.0001). CONCLUSIONS: In this model of OLV, BVV resulted in superior gas exchange and respiratory mechanics when compared with CMV. Improved static compliance persisted with restoration of two-lung ventilation.

Mathematical modelling to centre low tidal volumes following acute lung injury: a study with biologically variable ventilation.

BACKGROUND: With biologically variable ventilation [BVV--using a computer-controller to add breath-to-breath variability to respiratory frequency (f) and tidal volume (VT)] gas exchange and respiratory mechanics were compared using the ARDSNet low VT algorithm (Control) versus an approach using mathematical modelling to individually optimise VT at the point of maximal compliance change on the convex portion of the inspiratory pressure-volume (P-V) curve (Experimental). METHODS: Pigs (n = 22) received pentothal/midazolam anaesthesia, oleic acid lung injury, then inspiratory P-V curve fitting to the four-parameter logistic Venegas equation F(P) = a + b[1 + e-(P-c)/d]-1 where: a = volume at lower asymptote, b = the vital capacity or the total change in volume between the lower and upper asymptotes, c = pressure at the inflection point and d = index related to linear compliance. Both groups received BVV with gas exchange and respiratory mechanics measured hourly for 5 hrs. Postmortem bronchoalveolar fluid was analysed for interleukin-8 (IL-8). RESULTS: All P-V curves fit the Venegas equation (R2 > 0.995). Control VT averaged 7.4 +/- 0.4 mL/kg as compared to Experimental 9.5 +/- 1.6 mL/kg (range 6.6 - 10.8 mL/kg; p < 0.05). Variable VTs were within the convex portion of the P-V curve. In such circumstances, Jensen's inequality states "if F(P) is a convex function defined on an interval (r, s), and if P is a random variable taking values in (r, s), then the average or expected value (E) of F(P); E(F(P)) > F(E(P))." In both groups the inequality applied, since F(P) defines volume in the Venegas equation and (P) pressure and the range of VTs varied within the convex interval for individual P-V curves. Over 5 hrs, there were no significant differences between groups in minute ventilation, airway pressure, blood gases, haemodynamics, respiratory compliance or IL-8 concentrations. CONCLUSION: No difference between groups is a consequence of BVV occurring on the convex interval for individualised Venegas P-V curves in all experiments irrespective of group. Jensen's inequality provides theoretical proof of why a variable ventilatory approach is advantageous under these circumstances. When using BVV, with VT centred by Venegas P-V curve analysis at the point of maximal compliance change, some leeway in low VT settings beyond ARDSNet protocols may be possible in acute lung injury. This study also shows that in this model, the standard ARDSNet algorithm assures ventilation occurs on the convex portion of the P-V curve.

Fractal ventilation enhances respiratory sinus arrhythmia.

BACKGROUND: Programming a mechanical ventilator with a biologically variable or fractal breathing pattern (an example of 1/f noise) improves gas exchange and respiratory mechanics. Here we show that fractal ventilation increases respiratory sinus arrhythmia (RSA) -- a mechanism known to improve ventilation/perfusion matching. METHODS: Pigs were anaesthetised with propofol/ketamine, paralysed with doxacurium, and ventilated in either control mode (CV) or in fractal mode (FV) at baseline and then following infusion of oleic acid to result in lung injury. RESULTS: Mean RSA and mean positive RSA were nearly double with FV, both at baseline and following oleic acid. At baseline, mean RSA = 18.6 msec with CV and 36.8 msec with FV (n = 10; p = 0.043); post oleic acid, mean RSA = 11.1 msec with CV and 21.8 msec with FV (n = 9, p = 0.028); at baseline, mean positive RSA = 20.8 msec with CV and 38.1 msec with FV (p = 0.047); post oleic acid, mean positive RSA = 13.2 msec with CV and 24.4 msec with FV (p = 0.026). Heart rate variability was also greater with FV. At baseline the coefficient of variation for heart rate was 2.2% during CV and 4.0% during FV. Following oleic acid the variation was 2.1 vs. 5.6% respectively. CONCLUSION: These findings suggest FV enhances physiological entrainment between respiratory, brain stem and cardiac nonlinear oscillators, further supporting the concept that RSA itself reflects cardiorespiratory interaction. In addition, these results provide another mechanism whereby FV may be superior to conventional CV.

A comparison of biologically variable ventilation to recruitment manoeuvres in a porcine model of acute lung injury.

BACKGROUND: Biologically variable ventilation (return of physiological variability in rate and tidal volume using a computer-controller) was compared to control mode ventilation with and without a recruitment manoeuvre - 40 cm H2O for 40 sec performed hourly; in a porcine oleic acid acute lung injury model. METHODS: We compared gas exchange, respiratory mechanics, and measured bronchoalveolar fluid for inflammatory cytokines, cell counts and surfactant function. Lung injury was scored by light microscopy. Pigs received mechanical ventilation (FIO2 = 0.3; PEEP 5 cm H2O) in control mode until PaO2 decreased to 60 mm Hg with oleic acid infusion (PaO2/FIO2 <200 mm Hg). Additional PEEP to 10 cm H2O was added after injury. Animals were randomized to one of the 3 modes of ventilation and followed for 5 hr after injury. RESULTS: PaO2 and respiratory system compliance was significantly greater with biologically variable ventilation compared to the other 2 groups. Mean and mean peak airway pressures were also lower. There were no differences in cell counts in bronchoalveolar fluid by flow cytometry, or interleukin-8 and -10 levels between groups. Lung injury scoring revealed no difference between groups in the regions examined. No differences in surfactant function were seen between groups by capillary surfactometry. CONCLUSIONS: In this porcine model of acute lung injury, various indices to measure injury or inflammation did not differ between the 3 approaches to ventilation. However, when using a low tidal volume strategy with moderate levels of PEEP, sustained improvements in arterial oxygen tension and respiratory system compliance were only seen with BVV when compared to CMV or CMV with a recruitment manoeuvre.

Improved arterial oxygenation with biologically variable or fractal ventilation using low tidal volumes in a porcine model of acute respiratory distress syndrome.

We compared biologically variable ventilation (V (bv); n = 9) with control mode ventilation (V (c); n = 8) at low tidal volume (VT)--initial 6 ml/kg--in a porcine model of acute respiratory distress syndrome (ARDS). Hemodynamics, respiratory gases, airway pressures, and VT data were measured. Static P-V curves were generated at 5 h. Interleukin (IL)-8 and IL-10 were measured in serum and tracheal aspirate. By 5 h, higher Pa(O(2)) (173 +/- 30 mm Hg versus 119 +/- 23 mm Hg; mean +/- SD; p < 0.0001 group x time interaction [G x T]), lower shunt fraction (6 +/- 1% versus 9 +/- 3%; p = 0.0026, G x T) at lower peak airway pressure (21 +/- 2 versus 24 +/- 1 cm H(2)O; p = 0.0342; G x T) occurred with V (bv). IL-8 concentrations in tracheal aspirate and wet:dry weight ratios were inversely related; p = 0.011. With V (c), IL-8 concentrations were 3.75-fold greater at wet:dry weight ratio of 10. IL-10 concentrations did not differ between groups. In both groups, ventilation was on the linear portion of the P-V curve. With V (bv), VT variability demonstrated an inverse power law indicating fractal behavior. In this model of ARDS, V (bv) improved Pa(O(2)) at lower peak airway pressure and IL-8 levels compared with V (c).