Measuring the quality of therapeutic apheresis care in the pediatric intensive care unit.

Our goal was to measure the quality of care provided in the Pediatric Intensive Care Unit (PICU) during Therapeutic Apheresis (TA). We described the care as a step by step process. We designed a flow chart to carefully document each step of the process. We then defined each step with a unique clinical indictor (CI) that represented the exact task we felt provided quality care. These CIs were studied and modified for 1 year. We measured our performance in this process by the number of times we accomplished the CI vs. the total number of CIs that were to be performed. The degree of compliance, with these clinical indicators, was analyzed and used as a metric for quality by calculating how close the process is running exactly as planned or "in control." The Apheresis Process was in control (compliance) for 47% of the indicators, as measured in the aggregate for the first observational year. We then applied the theory of Total Quality Management (TQM) through our Design, Measure, Analyze, Improve, and Control (DMAIC) model. We were able to improve the process and bring it into control by increasing the compliance to > 99.74%, in the aggregate, for the third and fourth quarter of the second year. We have implemented TQM to increase compliance, thus control, of a highly complex and multidisciplinary Pediatric Intensive Care therapy. We have shown a reproducible and scalable measure of quality for a complex clinical process in the PICU, without additional capital expenditure.

Therapeutic hypercapnia enhances the inflammatory response to endotoxin in the lung of spontaneously breathing rats.

OBJECTIVE: To test the hypothesis that therapeutic hypercapnia enhances the proinflammatory responses to endotoxemia in the lung and spleen of rats. DESIGN: Prospective randomized study. SETTINGS: Hospital research institute. SUBJECTS: Forty-eight adult male rats. INTERVENTIONS: Rats were randomly assigned for a 24-hr period to four breathing groups (n = 11/group), including air (controls), normoxic air with 5% CO2 (therapeutic hypercapnia), air and endotoxemia (5 mg/kg endotoxin), and therapeutic hypercapnia with endotoxemia. After euthanasia, the lung and spleen were removed for pro- and anti-inflammatory cytokine analyses and pulmonary histology evaluation. Four additional rats were used to examine changes in gas exchange and acid-base balance during exposure to therapeutic hypercapnia with and without endotoxemia before and at 4, 12, and 24 hrs into the study, using a permanently catheterized femoral artery. MEASUREMENTS AND MAIN RESULTS: The ratios of proinflammatory cytokines (interleukin-1ß [IL-1ß] and IL-6) and an anti-inflammatory cytokine (IL-10) in the lungs and spleen were used as indices of inflammatory status. The wet-weight to dry-weight ratios, histologic changes in lung interstitial inflammation, and alveolar structures were used as indices of endotoxin-induced acute lung injury. IL-1ß and IL-6 expression was significantly high in the lung of therapeutic hypercapnia-treated endotoxemic rats compared to the lung of rats subjected to only endotoxemia (p < .05 and p < .001, respectively). In the spleen, therapeutic hypercapnia-treated endotoxemic rats had low expression of IL-1ß and IL-6 compared to rats subjected to only endotoxemia (p > .05 and p < .001). Therapeutic hypercapnia following endotoxemic challenge was associated with a proinflammatory response in the lung and an anti-inflammatory response in spleen, as assessed by the ratios of IL-1ß and IL-6 to IL-10. The wet-weight to dry-weight ratio and the interstitial space were significantly increased only in therapeutic hypercapnia-treated endotoxemic rats (p < .05). The alveolar-septal thickness was significantly increased by 21% in endotoxemic rats (p < .001) and by 33% in therapeutic hypercapnia-treated endotoxemic rats (p < .001). CONCLUSIONS: A 24-hr exposure to therapeutic hypercapnia in endotoxin-stimulated, spontaneously breathing rats is associated with a proinflammatory immune response in the lung and anti-inflammatory response in the spleen as well as an increase in certain histologic indices of endotoxin-induced lung injury.

Does hypercapnia ameliorate hyperoxia-induced lung injury in neonatal rats?

Therapeutic hypercapnia (TH), an intentional inhalation of CO(2), has been shown to improve pulmonary function in certain models of lung injury. We tested the null hypothesis that TH does not improve hyperoxic lung injury in neonatal rats. The prospective, randomized study was set at Research laboratory in Children's Hospital. Forty-five newborn rats were randomly assigned to three groups (n = 15/group), and exposed to 96 h of normoxia (FiO(2) = 0.21), hyperoxia (FiO(2) > 0.98), and TH (FiO(2) = 0.95, FiCO(2) = 0.05). Lung histology, wet-weight to dry-weight ratio, and concentrations of pro- and anti-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha, and IL-10) were used to evaluate pulmonary damage. Using a scale of 0-4, the total scores for lungs hypercellularity, inflammation, and hemorrhage was significantly increased from a median value of 1.5 in normoxia to 2.5 in hyperoxia (P < 0.05) and 3.0 with TH (P < 0.001, nonparametric ANOVA). The interstitial space relative to the alveolar space, as a measure of hypercellularity, was increased by 18% during hyperoxia and by 44% with TH compared with normoxia. TH significantly increased the size of the interstitial space by 22% compared with hyperoxia (P < 0.001). The lung wet-weight to dry-weight ratio was increased by 10% in both hyperoxic groups (P < 0.001). Both hyperoxic groups showed significant reductions in the concentration of IL-1beta compared with normoxia (P < 0.001), whereas the ratio of IL-1beta to IL-10 was significantly decreased, indicating an anti-inflammatory trend. TH does not prevent histological manifestations of hyperoxic lung injury in spontaneously breathing neonatal rats and may worsen the outcome.

Immunological response to (1,4)-alpha-D-glucan in the lung and spleen of endotoxin-stimulated juvenile rats.

We investigated the effects of (1,4)-alpha-D-glucan (alpha-DG), a novel immune stimulatory drug from Tinospora cordifolia, on the concentration of pro- and anti-inflammatory cytokines (interleukin [IL]-1beta, IL-6, tumour necrosis factor-alpha [TNF-alpha], gamma-interferon [IFN-gamma] and IL-10) in the lung and spleen of endotoxin-stimulated juvenile rats. Experimental groups (n = 16/group) included controls with an intraperitoneal injection of saline, endotoxaemic rats with a non-lethal dose of 10 mg/kg Escherichia coli endotoxin, and endotoxaemic rats treated with two doses of 10 mg/kg alpha-DG, intraperitoneally, 2 and 4 hr after endotoxin injection. At 24 hr of treatment, rats were euthanized and lungs and spleen were removed for cytokines determination and lung injury. Endotoxaemia increased IL-1beta concentration by fivefold in both organs, while creating a moderate pulmonary hypercellularity (demonstrated by about 11% increase in the alveolar-septal thickening and 11% decrease in the alveolar-interstitial space ratio). In the lung, alpha-DG treatment reduced concentrations of IL-1beta by 30% (p > 0.05), IL-6 by 43% (p < 0.01), IFN-gamma by 46% (p < 0.01) and the anti-inflammatory cytokine, IL-10, by 31% (p > 0.05) compared to endotoxaemia. In the spleen, alpha-DG treatment decreased the ratio of IL-1beta to IL-10 by 55% (p < 0.05), demonstrating an anti-inflammatory trend. These data suggest that alpha-DG differentially modulates cytokine response in the lung and spleen and modifies the pro- and anti-inflammatory balance during an early period of endotoxaemia in juvenile rats.

Drug use density in critically ill children and newborns: analysis of various methodologies.

OBJECTIVE: To compare in the pediatric, cardiac, and neonatal intensive care units, three methods of assessing vancomycin and linezolid drug use density by number of: defined daily doses (DDDs), prescribed daily doses, and days of drug use per 100 patient days. DESIGN: Retrospective study. SETTING: A tertiary care children's hospital. PATIENTS: We reviewed the charts of patients admitted to the cardiac intensive care unit and neonatal intensive care unit in 2005 who were treated with vancomycin, and those admitted to the pediatric intensive care unit who were treated with vancomycin or linezolid during 2004 and 2005. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The number of patients, treatment days, total amount of vancomycin/linezolid, total intensive care unit admissions, and patient days were recorded. We used the World Health Organization definition of DDD for vancomycin and linezolid (2000 and 1200 mg, respectively). The prescribed daily dose for each intensive care unit was calculated for each year by dividing the total amount of the medication administered by the total number of treatment days. The drug use densities were then calculated as the total DDDs, prescribed daily doses, and days of drug use per 100 patient days. The vancomycin use densities were significantly different among the three intensive care units when compared by each method. They were significantly lower in all three units when expressed as DDDs per 100 patient days. The vancomycin drug use density in the pediatric intensive care unit was significantly decreased during 2005 compared with 2004 by all three methods. CONCLUSIONS: In critically ill children, drug use density of vancomycin is significantly less when evaluated by the DDD method compared with the prescribed daily dose method, a more appropriate method in children. However, the simplest and most accurate method of assessing drug use density is the number of days of drug use method, which allows comparison of drug use density between different pediatric facilities or clinical units.

Physiological effects of a novel immune stimulator drug, (1,4)-α-D-glucan, in rats.

The (1,4)-α-D-glucan (α-D-glucan), derived from medicinal plant, Tinospora cordifolia, activates human lymphocytes with downstream synthesis of the pro- and anti-inflammatory cytokines, in vitro. We investigated physiological and immunological effects of a low and a high dose of α-D-glucan (0.5 and 10 mg/kg), in vivo, testing the hypothesis that intravenous administration of α-D-glucan does not affect haemodynamic, respiratory, haematological, and immune responses in normal rats. Male rats (300-400 g) were anaesthetized, tracheostomized, and catheterized in one femoral artery and vein. The mean arterial blood pressure and heart rate were continuously recorded. The baselines for gas exchange, differential blood cell count, and plasma concentration of TNF-α, IL-1ß, IL-4, IL-6, and IFN-γ were determined. Rats were then randomly assigned to controls (n = 7), a low dose (0.5 mg/kg; n = 10), and a high dose (10 mg/kg; n = 7) of α-D-glucan for a six 6 hr study period. Gas exchange, differential cell count, plasma concentration of TNF-α, IL-1ß, IL-4, IL-6, and IFN-γ, and mean arterial blood pressure values remained within physiological range. Intravenous administration of 10 mg/kg α-D-glucan created tachycardia, associated with hyperventilation, and significant reductions in the blood haemoglobin and haematocrit concentrations. We suggest that these in vivo effects of α-D-glucan should be considered for future clinical and/or experimental trials.

The effects of CO2 on cytokine concentrations in endotoxin-stimulated human whole blood.

OBJECTIVES: Hypercapnia is known to modulate inflammation in lungs. However, the effect of hypocapnia and hypercapnia on blood cytokine production during sepsis is not well understood. We hypothesized that CO2 modulates ex vivo inflammatory cytokine production during endotoxin stimulation. To test this hypothesis, we measured the production of pro- and anti-inflammatory cytokines in endotoxin-stimulated human whole blood cultures under hypercapnic, normocapnic, and hypocapnic conditions. DESIGN: Prospective randomized study. SETTING: Basic research laboratory. SUBJECTS: Ten male and 10 female volunteers. INTERVENTIONS: Venous blood samples, taken from volunteers were cultured at 37 degrees C, under hypocapnic (2% CO2), normocapnic (5% CO2), and hypercapnic (7% CO2) conditions, with and without endotoxin stimulation. After 24 hrs of incubation, each culture's supernatant was analyzed for tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-10, and interferon-gamma concentrations by enzyme-linked immunosorbent assay. Data were analyzed using nonparametric repeated measures of analysis of variance followed by Dunn's multiple comparisons test. Analysis of variance with Bonferroni correction was used to compare gender differences in cytokine concentrations. The Pearson test was used to estimate correlation between hydrogen ion and individual cytokine concentrations. MEASUREMENTS AND MAIN RESULTS: Concentrations of the proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta and of the anti-inflammatory cytokine interleukin-10 under hypercapnic condition were significantly decreased (p < 0.05, 0.01, and 0.001, respectively) for both genders when compared with either normocapnic or hypocapnic conditions. Concentrations of tumor necrosis factor-alpha and interleukin-1beta were significantly higher in men. In women, concentrations of interleukin-6 were significantly decreased under hypercapnic condition when compared with hypocapnic condition. An inverse relationship was found between hydrogen ion concentration and concentrations of tumor necrosis factor-alpha and interleukin-10. CONCLUSIONS: Our results are consistent with the hypothesis that CO2 can affect the production of pro- and anti-inflammatory cytokines after ex vivo stimulation with endotoxin.

Carbon dioxide clearance in rabbits during expiratory phase intratracheal pulmonary ventilation.

The purpose of this study was to compare the efficacy of CO2 removal during conventional mechanical ventilation (CMV) with and without expiratory phase intratracheal pulmonary ventilation (expiratory ITPV or Exp-ITPV); and to compare CO2 clearance during Exp-ITPV, in pressure-controlled ventilation (PCV) and in volume-controlled ventilation (VCV) modes. Seven anesthetized rabbits were tracheotomized and intubated using a 4 mm endotracheal tube. Venous and arterial lines were established. The rabbits were paralyzed, mechanically ventilated, and ventilation parameters were adjusted to achieve baseline arterial hypercapnia. Animals were then ventilated during 30-minute trials of CMV and Exp-ITPV, in both PCV and VCV modes. A custom-built, microprocessor-controlled solenoid valve was used to limit ITPV gas flow to the expiratory phase. Proximal and carinal airway pressures and hemodynamic variables were continuously recorded, and arterial blood gases were analyzed at the end of each trial. Exp-ITPV, as compared with CMV, reduced arterial PCO2 by 12% and 21% in PCV and VCV modes, respectively (p < 0.02 and p < 0.001; one-sided paired t test), without significant changes in other cardiorespiratory variables. In conclusion, Exp-ITPV is more effective than CMV in clearing CO2 through a small endotracheal tube. Exp-ITPV is also more effective in VCV mode than PCV mode.

Multiple-organ effect of normobaric hyperoxia in neonatal rats.

PURPOSE: Prolonged exposure to normobaric hyperoxia (NH) is associated with blood leukocyte activation and sequestration in the lung. Whether NH-induced leukocyte activation and sequestration can affect extrapulmonary organs or blood cellular profile has not been systematically investigated. We studied simultaneous changes in blood cellular profile and pulmonary, renal, and intestinal histology during NH and after return to air breathing ("weaning"). MATERIALS AND METHODS: One-day-old rats were exposed to 2 to 4 days of NH (FiO2 >0.98) or normoxia (FiO2 = 0.21), with or without weaning. Pups were then euthanized and 100 microL of blood was collected (cardiac puncture) for differential white blood cells analysis (n = 12 per group). The lungs, a piece of distal ileum, and the left kidney were removed for histologic evaluation. RESULTS: Both NH and weaning generated significant increases in blood neutrophil count, whereas lymphocyte population was significantly increased only after weaning (P < .05; analysis of variance with Bonferroni correction for multiple comparisons). Normobaric hyperoxia created mild increases in the renal tubular necrosis, dilation, regeneration, and interstitial inflammation. A significant increase in the intestinal serosal and submucosal vasodialation and vascularization occurred 1 day after weaning from 4 days of NH (P < .001). These extrapulmonary events coincided with the development of histologic manifestations of pulmonary oxygen toxicity. CONCLUSIONS: Development of pulmonary oxygen toxicity in neonatal rats is associated with significant changes in differential leukocyte counts and histologic alterations in the kidney and ileum. We speculate that activation of circulating leukocytes and/or direct effect of NH may affect certain peripheral organs independently from the NH-induced pulmonary pathology.

End-of-life decisions and palliative care in a children's hospital.

OBJECTIVE: To investigate clinical and demographic factors affecting the nature of end-of-life decisions and pediatric palliative care. DESIGN: Charts of 236 expired children were retrospectively reviewed for presence of endof- life care (EOLC) discussions and spiritual support, the nature of EOLC decisions, and the degree of opioid analgesics (OA) and sedatives (SDT) administration. RESULTS: Approximately 60% of patients had EOLC discussion, of whom 87.4% obtained an EOLC decision, mostly opting for withholding therapy (68.8%). Presence of EOLC discussion was associated with a longer hospital stay (univariate analyses: odds ratio [OR] = 1.9; p < 0.029), higher number of failed organs (OR = 2.5; p < 0.003), chronic illnesses (OR = 2.4; p < 0.002), spiritual support (OR = 1.8; p < 0.028) and respiratory diseases (OR = 3.1; p < 0.0006). Younger patients and those with higher number of failed organs were more likely to have withdrawal of therapy (OR = 10.9 and 6.0; p < 0.0001 and <0.002, respectively), whereas patients with chronic illness opted for withholding of therapy (OR = 3.1; p < 0.006). Spiritual support was associated with higher use of both OA and SDT (OR = 1.9 and 2.3; p < 0.014 and p < 0.005, respectively). Younger patients received less OA and SDT (OR = 0.2 and 0.4, respectively; p < 0.0001). Multivariate analyses showed that EOLC discussion is associated with higher use of OA and SDT (OR = 4.4 and 4.2; p < 0.00001 and p < 0.0001, respectively), whereas younger age is associated with withdrawal of therapy (OR = 8.3; p < 0.0005) and lower use of SDT (OR = 0.23; p < 0.0001). CONCLUSIONS: Patterns of care at the end of life vary in children with differing clinical and demographic characteristics. Because EOLC discussions are associated with greater focus on palliative care, strategies to enhance EOLC communications for pediatric patients should be further evaluated.

Hypoxic respiratory failure in term newborns: clinical indicators for inhaled nitric oxide and extracorporeal membrane oxygenation therapy.

PURPOSE: The criteria for starting extracorporeal membrane oxygenation (ECMO) therapy in term newborn patients with hypoxemic respiratory failure consist of an oxygenation index (OI) of 25 or higher and alveolar-arterial oxygen (Aao(2)) gradient of more than 600 at sea level. In such conditions, inhaled nitric oxide (iNO) may improve oxygenation and reduce the need for ECMO therapy. We studied early changes in OI and Aao(2) gradients in response to iNO treatment that may indicate a need to continue iNO treatment or the necessity to start an ECMO therapy. MATERIALS AND METHODS: In this prospective study, we used 34 outborn neonatal patients that were referred to our pediatric critical care unit in a children's hospital for ECMO therapy with diagnosis of hypoxemic respiratory failure. In all patients, iNO therapy, starting at 80 ppm, was instituted either during transport or on arrival to hospital. Response to iNO was assessed after 1 hour, at which time, iNO concentration was reduced to 40 ppm, provided there was more than 20% improvement in either or both oxygenation indices. Patients who did not respond positively to continuous iNO therapy and met ECMO criteria were given ECMO therapy. RESULTS: Inhaled nitric oxide therapy alone was successful in 10 (29%) of 34 patients. Eighteen patients (53%) required ECMO therapy within the first 10 hours of iNO treatment (early ECMO therapy), whereas 6 other neonates (18%) became eligible for ECMO therapy after prolonged (2-4 days) iNO treatment (late ECMO therapy). No mortality occurred with any treatment. Within 4 hours after iNO therapy, patients who required early ECMO therapy had significantly higher OI and Aao(2) gradients than patients who were treated with iNO therapy alone (P<.01, analysis of variance followed by Tukey-Kramer multiple comparison test). Six of 34 patients (18%), categorized as late ECMO therapy, on the average, had initially higher levels of OI and mean airway pressure than neonates in iNO treatment and early ECMO therapy. CONCLUSION: Persisting levels of OI of more than 20 or Aao(2) gradients of more than 600 after 4 hours of iNO therapy could be indicative of an immediate need for ECMO therapy.

Cardiovascular stability during arteriovenous extracorporeal therapy: a randomized controlled study in lambs with acute lung injury.

INTRODUCTION: Clinical application of arteriovenous (AV) extracorporeal membrane oxygenation (ECMO) requires assessment of cardiovascular ability to respond adequately to the presence of an AV shunt in the face of acute lung injury (ALI). This ability may be age dependent and vary with the experimental model. We studied cardiovascular stability in a lamb model of severe ALI, comparing conventional mechanical ventilation (CMV) with AV-ECMO therapy. METHODS: Seventeen lambs were anesthetized, tracheotomized, paralyzed, and ventilated to maintain normocapnia. Femoral and jugular veins, and femoral and carotid arteries were instrumented for the AV-ECMO circuit, systemic and pulmonary artery blood pressure monitoring, gas exchange, and cardiac output determination (thermodilution technique). A severe ALI (arterial oxygen tension/inspired fractional oxygen <200) was induced by lung lavage (repeated three times, each with 5 ml/kg saline) followed by tracheal instillation of 2.5 ml/kg of 0.1 N HCl. Lambs were consecutively assigned to CMV treatment (n = 8) or CMV plus AV-ECMO therapy using up to 15% of the cardiac output for the AV shunt flow during a 6-hour study period (n = 9). The outcome measures were the degree of inotropic and ventilator support needed to maintain hemodynamic stability and normocapnia, respectively. RESULTS: Five of the nine lambs subjected to AV-ECMO therapy (56%) died before completion of the 6-hour study period, as compared with two out of eight lambs (25%) in the CMV group (P > 0.05; Fisher's exact test). Surviving and nonsurviving lambs in the AV-ECMO group, unlike the CMV group, required continuous volume expansion and inotropic support (P < 0.001; Fisher's exact test). Lambs in the AV-ECMO group were able to maintain normocapnia with a maximum of 30% reduction in the minute ventilation, as compared with the CMV group (P < 0.05). CONCLUSION: AV-ECMO therapy in lambs subjected to severe ALI requires continuous hemodynamic support to maintain cardiovascular stability and normocapnia, as compared with lambs receiving CMV support.

Effect of aerosolized milrinone during drug-induced pulmonary hypertension in lambs.

We tested whether aerosolized milrinone in lambs selectively reduces drug-induced acute pulmonary hypertension without reducing the mean systemic blood pressure (MSBP). Seven, 2-3-week-old lambs were anesthetized (50 mg/kg ketamine), paralyzed (0.1 mg/kg vecuronium bromide) and mechanically ventilated. A femoral artery, pulmonary artery, and jugular vein were catheterized for continuous monitoring of MSBP, mean pulmonary artery pressure, periodic gas-exchange analyses, and determination of cardiac output by thermodilution technique. An Airlife Misty nebulizer was used in a dry state to establish a stable baseline of an inspired fraction of oxygen (FiO(2)) at 0.21. Acute pulmonary hypertension with hypoxemia was then induced by increasing the mean pulmonary artery pressure up to 30-35% of the MSBP using 2-6 microg/kg/min of Thromboxane A(2) mimetic (U-46619), intravenously. The lambs were then subjected to 15 min of saline nebulization without milrinone followed by 30 min saline nebulization with a relatively high concentration of milrinone (10 mg/ml, total dose of 40 mg). Aerosolized milrinone had no effect on systemic or pulmonary artery pressure during combined acute pulmonary hypertension and hypoxemia. We speculate that our nebulization procedures failed to deliver sufficient amount of milrinone for producing a detectable hemodynamic effect.

Aminophylline therapy during endotoxemia in anesthetized spontaneously breathing rats.

Phosphodiesterase inhibitors, such as pentoxifylline and aminophylline, may reduce inflammatory cytokine-induced endothelial permeability. We tested the hypothesis that aminophylline treatment may ameliorate the pulmonary and extrapulmonary effects of endotoxemia in a rat model. In anesthetized rats, a tracheotomy was performed along with catheterization of a femoral vein and artery. Anesthesia, fluid balance, and normothermia were maintained throughout the 6-h experiment. A stable hemodynamic and gas-exchange baseline was established at which time the rats were randomly divided into three groups. Group I received aminophylline (1mg/kg) over 30 min followed by 0.5mg/kg/h. Group II received a single dose of endotoxin (4 mg/kg) while Group III received both aminophylline and endotoxin as described for Groups I and II, respectively. Gas-exchange profiles, mean arterial blood pressure, and heart rate were determined every 2h. At hour 6, the rats were euthanized and lung, kidney, and heart tissue were removed for determination of water content. As our control group, we utilized data from our previously published study involving an identical surgical procedure with normal saline. Endotoxemia produced characteristic respiratory and hemodynamic signs of sepsis including hypotension, hyperventilation, tachycardia, and renal and pulmonary edema. Aminophylline treatment failed to prevent these endotoxemia-induced respiratory and hemodynamic manifestations of sepsis, but significantly improved the acid-base imbalance that developed during surgical procedures in saline-treated control rats. Further studies are warranted to determine potentially beneficial doses of aminophylline and resulting theophylline serum concentrations under such septic conditions.

Esophageal capnometry during hemorrhagic shock and after resuscitation in rats.

BACKGROUND: Splanchnic perfusion following hypovolemic shock is an important marker of adequate resuscitation. We tested whether the gap between esophageal partial carbon dioxide tension (PeCO2) and arterial partial carbon dioxide tension (PaCO2) is increased during graded hemorrhagic hypotension and reversed after blood reinfusion, using a fiberoptic carbon dioxide sensor. MATERIALS AND METHOD: Ten Sprague-Dawley rats were anesthetized, tracheotomized, and cannulated in one femoral artery and vein. A calibrated fiberoptic PCO2 probe was inserted into the distal third of the esophagus for determination of luminal PeCO2 during maintained anesthesia (pentobarbital 15 mg/kg per hour), normothermia (38 +/- 0.5 degrees C), and fluid balance (saline 5 ml/kg per hour). Three out of 10 rats were used to determine the limits of hemodynamic stability during gradual hemorrhage. Seven of the 10 rats were then subjected to mild and severe hemorrhage (15 and 20-25 ml/kg, respectively). Thirty minutes after severe hemorrhage, these rats were resuscitated by reinfusion of the shed blood. Arterial gas exchange, hemodynamic variables, and PeCO2 were recorded at each steady-state level of hemorrhage (at 30 and 60 min) and after resuscitation. RESULTS: The PeCO2-PaCO2 gap was significantly increased after mild and severe hemorrhage and returned to baseline (prehemorrhagic) values following blood reinfusion. Base deficit increased significantly following severe hemorrhage and remained significantly elevated after blood reinfusion. Significant correlations were found between base deficit and PeCO2-PaCO2 (P < 0.002) and PeCO2 (P < 0.022). Blood bicarbonate concentration decreased significantly following mild and severe hemorrhage, but its recovery was not complete at 60 min after blood reinfusion. CONCLUSION: Esophageal-arterial PCO2 gap increases during graded hemorrhagic hypotension and returns to baseline value after resuscitation without complete reversal of the base deficit. These data suggest that esophageal capnometry could be used as an alternative for gastric tonometry during management of hypovolemic shock.

Tracheobronchial injury during intratracheal pulmonary ventilation in rabbits.

OBJECTIVE: We compared tracheobronchial injury following short-term intratracheal pulmonary ventilation (ITPV) and conventional mechanical ventilation (CMV) in a healthy rabbit model. ITPV, a form of tracheal gas insufflation, has been shown to decrease deadspace ventilation and increase CO2 removal and therefore may reduce ventilator-induced lung injury. SETTING: Medical center laboratory. SUBJECTS: Twenty-five rabbits. INTERVENTIONS: Rabbits were randomly assigned to either ITPV or CMV (n = 15 and 10, respectively). Both groups were mechanically ventilated for 8 hrs at the same ventilator settings (FIO2, 0.4; rate, 30 breaths/min; flow, 4 L x min(-1); positive end-expiratory pressure, 4 cm H2O; tidal volume, 40 mL). Peak, mean, and end-expiratory carinal pressures, ITPV flow rate, and hemodynamic variables were continuously monitored. Tissue samples for histologic analysis were obtained postmortem from the trachea contiguous to the tip of the endotracheal tube, the distal trachea, the carina, and the main bronchus. The histologic sections were scored, in a single-blind fashion, for ciliary damage, ulceration, hemorrhage, overall inflammation, intraepithelial inflammatory infiltrate, and edema. MEASUREMENTS AND MAIN RESULTS: ITPV was associated with significantly lower Paco and deadspace ventilation ratio than CMV. The combined tracheobronchial injury scores for all samples were significantly higher in the ITPV group compared with the CMV group (p <.005; Mann-Whitney U test). The ITPV injury scores, compared with CMV injury scores, were significantly higher at the carina and main bronchus (p <.01; Kruskal-Wallis test followed by Dunn's multiple comparison test). The area adjacent to the endotracheal tube showed the same degree of damage in both groups. Analysis of the injury scores in individual damage categories demonstrated the greatest difference in the ulceration category (p <.001). CONCLUSIONS: In our study, ITPV, compared with CMV at the same minute ventilation, was associated with a significantly greater difference in tracheobronchial damage at the carina and main bronchus. We postulate that this difference may have been caused by the turbulence of the gas flow generated by the small-caliber ITPV catheter used in our neonatal-size animal model.