Oral Care Associated With Less Microaspiration in Ventilated Cardiac Patients.

Aspiration is common in mechanically ventilated patients and may predispose patients to aspiration pneumonia, chemical pneumonitis, and chronic lung damage. Pepsin A is a specific marker of gastric fluid aspiration and is often detected in ventilated pediatric patients. We investigated the effect of oral care and throat suctioning in the detection of pepsin A in tracheal aspirates (TAs) up to 4 hours after these procedures. Methods: Twelve pediatric patients between age 2 weeks to 14 years who underwent intubation for cardiac surgery were enrolled in this study. Six of the 12 patients were consented before their surgery with initial specimen collected at the time of intubation and last one shortly before extubation (intubation duration < 24 hours). The remaining 6 patients were consented after cardiac surgery. All specimens were collected per routine care per respiratory therapy protocol and shortly before extubation (intubation duration > 24 hours). Tracheal fluid aspirates were collected every 4 to 12 hours in the ventilated patients. Enzymatic assay for gastric pepsin A and protein determination were performed. The time of oral care and throat suctioning within 4 hours prior was recorded prospectively. Results: A total of 342 TA specimens were obtained from the 12 intubated pediatric patients during their course of hospitalization; 287 (83.9%) showed detectable total pepsin (pepsin A and C) enzyme activity (> 6 ng/mL) and 176 (51.5%) samples had detectable pepsin A enzyme levels (>6 ng/mL of pepsin A). Only 29 samples of 76 samples (38.2%) had evidence of microaspiration after receiving oral care, while 147 of 266 (55.3%) samples were pepsin A positive when no oral care was provided. Odds ratio is 0.50 (Cl 0.30-0.84), and the number needed to treat is 5.8 (Confidence interval 3.4-22.3). Testing air filters for pepsin was not beneficial. Conclusion: Oral care is a highly effective measure to prevent microaspiration of gastric fluid in ventilated pediatric patients. The number needed to treat (5.8) suggests this is a very effective prevention strategy. Our study suggests that pepsin A is a useful and sensitive biomarker that allows identification of gastric aspiration.

Passive Peritoneal Drainage Impact on Fluid Balance and Inflammatory Mediators: A Randomized Pilot Study.

BACKGROUND: Infants after cardiopulmonary bypass are exposed to increasing inflammatory mediator release and are at risk of developing fluid overload. The aim of this pilot study was to evaluate the impact of passive peritoneal drainage on achieving negative fluid balance and its ability to dispose of inflammatory cytokines. METHODS: From September 2014 to November 2016, infants undergoing STAT category 3, 4, and 5 operations were randomized to receive or not receive intraoperative prophylactic peritoneal drain. We analyzed time to negative fluid balance and perioperative variables for each group. Pro- and anti-inflammatory cytokines were measured from serum and peritoneal fluid in the passive peritoneal drainage group and serum in the control group postoperatively. RESULTS: Infants were randomized to prophylactic passive peritoneal drain group (n = 13) and control (n = 12). The groups were not significantly different in pre- and postoperative peak lactate levels, postoperative length of stay, and mortality. Peritoneal drain patients reached time to negative fluid balance at a median of 1.42 days (interquartile range [IQR]: 1.00-2.91), whereas the control at 3.08 (IQR: 1.67-3.88; P = .043). Peritoneal drain patients had lower diuretic index at 72 hours, median of 2.86 (IQR: 1.21-4.94) versus 6.27 (IQR: 4.75-11.11; P = .006). Consistently, tumor necrosis factor-α, interleukin (IL)-4, IL-6, IL-8, IL-10, and interferon-γ were present at higher levels in peritoneal fluid than serum at 24 and 72 hours. However, serum cytokine levels in peritoneal drain and control group, at 24 and 72 hours postoperatively, did not differ significantly. CONCLUSIONS: The prophylactic passive peritoneal drain patients reached negative fluid balance earlier and used less diuretic in early postoperative period. The serum cytokine levels did not differ significantly between groups at 24 and 72 hours postoperatively. However, there was no significant difference in mortality and postoperative length of stay.

Risk Factors for Gastrostomy Tube Placement in Single Ventricle Patients Following The Norwood Procedure.

Neonates with single ventricle heart disease frequently experience poor oral feeding and inconsistent weight gain, often requiring gastrostomy tube (gtube) placement. We sought to identify risk factors for gtube placement in neonates following the Norwood procedure at our institution. We retrospectively reviewed multiple preoperative, operative, and postoperative variables in neonates <30 days with single ventricle heart disease following the Norwood procedure. Study outcomes included duration of mechanical ventilation, hospital length of stay (HLOS), and gtube requirement. Multivariable logistic regression was used to analyze for associated risk factors. Seventy-nine neonates were included in the study, of which 47 underwent gtube placement (59.5%). Multivariable regression analysis found vocal cord dysfunction (P = 0.001, odds ratio 1.1, 95% confidence interval 1.0-1.4) and longer duration of sedative or narcotic infusion (P = 0.01, odds ratio 1.1, 1.03-1.2) to be independently associated with the requirement for gtube among patients who underwent the Norwood procedure. There was a significant difference in HLOS (median 69 vs 33, P = 0.003) between the gtube and the no gtube groups. Univariate analysis comparing the era of surgery was performed and found a significant difference between the groups in terms of the number of gtubes placed (P = 0.02) and duration of sedative or narcotic infusion days (P = 0.038). Both were greater in the era from 2011 to 2015. In a single-institution analysis of neonates following the Norwood procedure, gtube requirement was independently associated with vocal cord dysfunction and longer duration of sedative or narcotic infusions. gtube placement was also associated with longer HLOS.

Inadequate preoperative nutrition might be associated with acute kidney injury and greater illness severity postoperatively.

OBJECTIVE: Nutrition is vital for maintaining optimal cellular and organ function, particularly in neonates who undergo cardiac surgery. Achieving nutritional goals preoperatively can be challenging because of fluid restrictions, suboptimal oral intake, and concerns for inadequate gastrointestinal circulation. We examined preoperative caloric intake and its effects on postoperative course in neonates who underwent cardiac surgery. METHODS: We retrospectively reviewed records of neonates (younger than 30 days) who underwent congenital heart surgery requiring cardiopulmonary bypass from 2008 to 2014 at Arnold Palmer Hospital for Children. Data on multiple nutritional and postoperative variables were collected. Study outcomes included hospital length of stay, duration of mechanical ventilation, and acute kidney injury (AKI). RESULTS: Records of 95 neonates were reviewed. Sixty-six patients (69.5%) with a median age of 5 days did not achieve preoperative caloric goal, whereas 29 patients (30.5%) with a median age of 11 days did. Of those who achieved caloric goal, 6 (20.6%) achieved it via total parental nutrition, 9 (31.1%) with a combination of total parental nutrition and enteral feeds, and 14 (48.3%) via enteral route. There was a significant difference in peak lactate (P = .002), inotropic score (P = .02), and duration of mechanical ventilation (P = .013) between those who did and did not achieve caloric goal. In multivariable analysis we found that failure to achieve caloric goal preoperatively was independently associated with stage 2 or 3 AKI (P = .04; odds ratio, 4.48; 95% confidence interval, 1.02-19.63) and younger age at the time of surgery (P < .001; odds ratio, 0.12; 95% confidence interval, 0.04-0.33). CONCLUSIONS: Failure to achieve preoperative caloric goal might contribute to development of AKI and might be associated with greater severity of illness postoperatively.

Recurrent Laryngeal Nerve Injury and Swallowing Dysfunction in Neonatal Aortic Arch Repair.

BACKGROUND: We evaluated the incidence, clinical effect, and recovery rate of vocal cord dysfunction (VCD) and swallowing dysfunction in neonates undergoing aortic arch repair. METHODS: We retrospectively evaluated 101 neonates who underwent aortic arch reconstruction from 2008 to 2015. Direct flexible laryngoscopy was performed in 89 patients before initiation of postoperative oral feeding after Norwood (n = 63) and non-Norwood (n = 26) arch reconstruction. We defined VCD as immobility of vocal cords or their lack of coaptation and poor mobility. RESULTS: The incidence of VCD after aortic arch repair was 48% (n = 43). There was no significant difference between the VCD and non-VCD groups in postoperative length of stay, extubation failure, cardiopulmonary bypass, cross-clamp, selective cerebral perfusion time, operative death, and The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) Congenital Heart Surgery Mortality Categories. Placement of gastrostomy (p = 0.03) and documented aspiration (p = 0.01) were significantly more common in VCD patients. The incidence of VCD was 41% (n = 26) after Norwood and 65% (n = 17) after non-Norwood repairs (p = 0.06). Gastrostomy was required in 44 Norwood patients vs 9 non-Norwood patients (p = 0.004). Median length of stay was similar in Norwood patients with or without VCD (p = .28) but was significantly longer in non-Norwood patients with VCD vs those without (p = 0.002). At follow-up direct flexible laryngoscopy, VCD recovery was 74% (14 of 19) in the Norwood group and 86% (12 of 14) in the non-Norwood group. CONCLUSIONS: The incidence of VCD and swallowing dysfunction in neonates undergoing aortic arch reconstruction is high. Patients with VCD have a significantly higher incidence of gastrostomy placement and aspiration. In the Norwood population, length of stay is not associated with presence or absence of VCD. More than 70% of patients in each group who had direct flexible laryngoscopy follow-up recovered vocal cord function.

Single institution experience with the Ladd's procedure in patients with heterotaxy and stage I palliated single-ventricle.

AIM: To investigate and describe our current institutional management protocol for single-ventricle patients who must undergo a Ladd's procedure. METHODS: We retrospectively reviewed the charts of all patients from January 2005 to March 2014 who were diagnosed with heterotaxy syndrome and an associated intestinal rotation anomaly who carried a cardiac diagnosis of functional single ventricle and were status post stage I palliation. A total of 8 patients with a history of stage I single-ventricle palliation underwent Ladd's procedure during this time period. We reviewed each patients chart to determine if significant intraoperative or post-operative morbidity or mortality occurred. We also described our protocolized management of these patients in the cardiac intensive care unit, which included pre-operative labs, echocardiography, milrinone infusion, as well as protocolized fluid administration and anticoagulation regimines. We also reviewed the literature to determine the reported morbidity and mortality associated with the Ladd's procedure in this particular cardiac physiology and if other institutions have reported protocolized care of these patients. RESULTS: A total of 8 patients were identified to have heterotaxy with an intestinal rotation anomaly and single-ventricle heart disease that was status post single ventricle palliation. Six of these patients were palliated with a Blaylock-Taussig shunt, one of whom underwent a Norwood procedure. The two other patients were palliated with a stent, which was placed in the ductus arteriosus. These eight patients all underwent elective Ladd's procedure at the time of gastrostomy tube placement. Per our protocol, all patients remained on aspirin prior to surgery and had no period where they were without anticoagulation. All patients remained on milrinone during and after the procedure and received fluid administration upon arrival to the cardiac intensive care unit to account for losses. All 8 patients experienced no intraoperative or post-operative complications. All patients survived to discharge. One patient presented to the emergency room two months after discharge in cardiac arrest and died due to bowel obstruction and perforation. CONCLUSION: Protocolized intensive care management may have contributed to favorable outcomes following Ladd's procedure at our institution.

Culture Negative Stent Infection in an Infant with Hypoplastic Left Heart and Persistent Fever.

We present an infant with hypoplastic left heart with persistent fever despite two courses of antibiotics and repeatedly negative blood cultures. He eventually underwent surgical extraction of two stents. The stent cultures became positive; he was treated with 4 weeks of antibiotics and the fever resolved.

Are We Overdiagnosing Acute Kidney Injury in Pediatric Patients Following Cardiac Surgery?

BACKGROUND: The use of two diagnostic criteria in the current literature has led to some degree of ambiguity in the precise diagnosis of acute kidney injury in pediatric patients undergoing surgery for congenital heart disease. This study aims to determine which criteria is the most accurate diagnostic indicator of acute kidney injury and determine whether the incidence is being overestimated based on the current criteria. METHODS: This retrospective study consisted of 389 patients with congenital heart disease from birth to 18 years, who underwent cardiac surgery. The statistical tests conducted were the student t test and chi-square test. Outcomes measured included hospital length of stay, duration of mechanical ventilation, and mortality. RESULTS: The incidence rate of acute kidney injury diagnosed by the pediatric Risk, Injury, Failure, Loss, and End-Stage Renal Disease (RIFLE) criterion was 56% compared to 24.4% for the Acute Kidney Injury Network criterion. The pediatric RIFLE criterion consists of the following subsets: risk, injury, failure, loss, and end-stage renal disease. Patients classified in the "risk" subset of the pediatric RIFLE criterion who failed to meet Acute Kidney Injury Network criterion were compared to patients without acute kidney injury. Comparison of intensive care unit outcomes between these groups lacked statistical significance for all variables except the duration of mechanical ventilation postoperatively. CONCLUSION: Although recent research in this field identified the pediatric RIFLE criterion as the most sensitive indicator of acute kidney injury, the results of this study suggest the pediatric RIFLE criterion overestimates acute kidney injury incidence and that the Acute Kidney Injury Network criterion is the more accurate diagnostic indicator.

Acute Kidney Injury and Fluid Overload in Neonates Following Surgery for Congenital Heart Disease.

BACKGROUND: Acute kidney injury (AKI) and fluid overload have been shown to increase morbidity and mortality. The reported incidence of AKI in pediatric patients following surgery for congenital heart disease is between 15% and 59%. Limited data exist looking at risk factors and outcomes of AKI or fluid overload in neonates undergoing surgery for congenital heart disease. METHODS: Neonates aged 6 to 29 days who underwent surgery for congenital heart disease and who were without preoperative kidney disease were included in the study. The AKI was determined utilizing the Acute Kidney Injury Network criteria. RESULTS: Ninety-five neonates were included in the study. The incidence of neonatal AKI was 45% (n = 43), of which 86% had stage 1 AKI. Risk factors for AKI included cardiopulmonary bypass time, selective cerebral perfusion, preoperative aminoglycoside use, small kidneys by renal ultrasound, and risk adjustment for congenital heart surgery category. There were eight mortalities (five from stage 1 AKI group, three from stage 2, and zero from stage 3). Fluid overload and AKI both increased hospital length of stay and postoperative ventilator days. CONCLUSION: To avoid increased risk of morbidity and possibly mortality, every attempt should be made to identify and intervene on those risk factors, which may be modifiable or identifiable preoperatively, such as small kidneys by renal ultrasound.

Intra-operative arrhythmia predicts post-operative arrhythmia and the need for temporary pacing wires.

OBJECTIVE: Protocols for the placement of temporary pacing wires vary among institutions. Our current protocol is to selectively place temporary pacing wires in those patients who develop haemodynamically significant intra-operative arrhythmia. We wished to identify how effective our current protocol is at identifying who will develop post-operative arrhythmia and need temporary pacing wires. METHODS: The charts of 880 patients over 8 years who underwent cardiopulmonary bypass were reviewed to find patients who developed intra-operative arrhythmia, had temporary pacing wires placed, and whether or not they developed post-operative arrhythmia and required utilisation of the pacing wires. RESULTS: A total of 87 (9.9%) out of 880 patients who required cardiopulmonary bypass over 8 years had intra-operative arrhythmia and had temporary pacing wires placed. Of these, 59 (67.8%) had post-operative arrhythmia and utilised the pacing wires, whereas 28 (32.2%) did not have post-operative arrhythmia or utilise the pacing wires. In all, seven patients who did not have intra-operative arrhythmia or temporary pacing wires placed developed post-operative arrhythmia. CONCLUSION: Intra-operative arrhythmia is predictive of post-operative arrhythmia (70.2%) and our protocol is a sensitive means of identifying those who will develop post-operative arrhythmia (89.3%).

Influence of a dedicated paediatric cardiac intensive care unit on patient outcomes.

BACKGROUND: The impact of a designated intensive care unit (ICU) for postoperative cardiac care in children is not clear. In our hospital (in the USA), we started a new Paediatric Cardiac Surgery programme 5 years ago, in September 2004. During the first 2 years of the programme, postoperative care was accomplished within the general paediatric ICU (PICU or c-ICU). Subsequently, in September 2006, a dedicated cardiac ICU (d-ICU) was established. We looked at our experience during these two periods to determine whether the designation of a separate ICU affected outcomes for these children. DESIGN AND METHODS: We obtained Institutional Review Board (IRB) approval to review the medical records for all postoperative cardiac admissions to the ICU during the first 4 years of the programme (September 2004-September 2008). Variables collected included age, gender, diagnosis, type of cardiac surgery, Risk Adjustment for Congenital Cardiac Surgery, version 1 (RACHS-1) classification, ventilator use, hospital stay, invasive line infections, ventilator-related infections, wound infections, need for cardiopulmonary support, return to the operating room, re-exploration of the chest, delayed sternal closure, accidental extubations, re-intubation and mortality rates. These variables were summed and compared for the combined PICU and the dedicated paediatric cardiac ICU. RESULTS: There were 199 cases performed in the first 2 years compared with 244 in the following 2 years. We saw a statistically insignificant increase in the number and complexity of cases during the second period (p = 0·08). However, morbidity declined as evidenced by the decrease in wound infection (p < 0·001) and need for chest re-exploration (p < 0·001). In addition, mortality declined from 7 of 199 (3·5%) to 2 of 244 (0·8%). p < 0·04 and less children required resuscitation (p < 0·01). CONCLUSIONS: We believe the designation of a specific area for postoperative cardiac care was instrumental in the growth and development of our cardiac programme. This rapid change accomplished several crucial elements that lead to accelerated improvement in patient care and a decline in morbidity and mortality.

Transport of critically ill children on cardiopulmonary support assistance.

OBJECTIVE: To report two patients helicopter transport on mechanical cardiopulmonary support to a transplant center. SETTING: Cardiac intensive care unit (CICU) and transport helicopter. PATIENTS: A 9 kg and 22 kg children who suffer cardiac deterioration needing air transport on mechanical cardiopulmonary support. INTERVENTIONS AND RESULTS: CPS was initiated to support these patients failing cardiac function. Transport on CPS of these two patients to a transplant institution was accomplished after determining that heart transplantation would be their more likely chance for recovery. CONCLUSION: A cardiac deterioration event that will lead to the need for heart transplantation can be acute and sudden sparing no time for early referral to a transplant center. It is necessary for heart centers to have a plan of action to provide inter-hospital transport on cardiopulmonary support (CPS). This protocol can involve transport by the referral institution, the receiving institution or a third institution.

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.

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.

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.

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.