Over-the-Wire Intravascular Ultrasound in an Animal Model of Pulmonary Hypertension

ABSTRACT

Background: Intravascular ultrasound (IVUS) measures prognostically important pulsatile flow indexes in patients with pulmonary hypertension (PH). IVUS catheters traditionally require a guiding catheter for placement which can impact hemodynamics in small infants because the guiding catheter renders the atrioventricular valve incompetent. Methods: Domestic swine (1.4–2.2 kg) were raised in isobaric normoxia (n = 4) or hypoxia (n = 3, FiO₂ 10–12%) for 72 hr for induction of PH. Cardiac catheterization and intravascular imaging was performed using a 3.5-Fr 20-MHz Eagle Eye Gold catheter (Volcano Corp., CA, USA) over a 0.014′′ guide wire. Intima-media thickness (IMT) was measured and relative area change and vascular pulsatility were calculated. Results: The IVUS probe was easily manipulated over a 0.014′′ wire without hemodynamic compromise in all animals. The IMT was thicker in the hypoxic group than the normoxic group (0.19 ± 0.03 mm vs. 0.31 ± 0.04 mm, p = .067). Hypoxic animals had systolic PH (39.66 ± 2.51 vs. 21.75 ± 2.87 mmHg, p = .02). Systemic arterial pressures between the groups were the same (hypoxic 68 ± 10.44 vs. normoxic 79.75 ± 14.84 mmHg, p = .26). Vascular pulsatility was similar (hypoxic 24 ± 2.64 vs. 20.25 ± 0.57%, p = .18). However, the arterial wall distensibility was significantly different (0.98 ± 0.2 vs. 2.01 ± 1.38 %/mmHg, p = .04). Conclusions: Monorail IVUS imaging without a guide catheter overcomes a major limitation for use in infants and small animal experimental models by avoiding hemodynamic compromise. This would be a valuable tool for assessment of PH in the research and clinical setting.     

Veno-Venous Extracorporeal Membrane Oxygenation (VV ECMO) for Acute Respiratory Failure Following Injury: Outcomes in a High-Volume Adult Trauma Center with a Dedicated Unit for VV ECMO

Introduction

The use of veno-venous extracorporeal membrane oxygenation (VV ECMO) has increased over the past decade. The purpose of this study was to evaluate outcomes in adult trauma patients requiring VV ECMO.

Methods

Data were collected on adult trauma patients admitted between January 1, 2015, and November 1, 2016. Demographics, injury-specific data, ECMO data, and survival to discharge were recorded. Medians [interquartile range (IQR)] were reported. A p value ≤0.05 was considered statistically significant.

Results

Eighteen patients required VV ECMO during the study period. Median age was 28.5 years (IQR 24–43). Median injury severity score (ISS) was 27 (IQR 21–41); median PaO₂/FiO₂ (P/F) prior to ECMO cannulation was 61 (IQR 50–70). Median time from injury to cannulation was 3 (IQR 0–6) days. Median duration of ECMO was 266 (IQR 177–379) hours. Survival to discharge was 78%. Survivors had a significantly higher ISS (p = 0.03), longer intensive care unit length of stay (ICU LOS) (p < 0.0004), hospital LOS (p < 0.000004), and time on the ventilator (p < 0.0003). Median time of injury to cannulation was significantly longer in patients who survived to discharge (p = 0.01). There was no difference in P/F ratio prior to cannulation (p = ns).

Conclusion

We have demonstrated improved outcome of patients requiring VV ECMO following injury compared to historical data. Although shorter time from injury to cannulation for VV ECMO was associated with death, select patients who meet criteria for VV ECMO early following injury should be referred/transferred to a tertiary care facility that specializes in trauma and ECMO care.

     

Venovenous versus venoarterial extracorporeal membrane oxygenation in congenital diaphragmatic hernia

Background: Extracorporeal membrane oxygenation (ECMO) has a significant role as a final rescue modality in severe respiratory failure of the newborn with congenital diaphragmatic hernia (CDH). The objective of this study was to compare the efficiency of venovenous (VV) versus venoarterial (VA) ECMO in newborns with CDH.Methods: A retrospective report of 11 years experience (1990 through 2001) of a single center, comparing VV and VA ECMO is given. VV ECMO was the preferred rescue modality for respiratory failure unresponsive to maximal medical therapy. Only when the placement of a VV ECMO 14F catheter was not possible, VA ECMO was used. Forty-six patients met ECMO criteria; 26 were treated with VV ECMO and 19 with VA ECMO. One patient underwent conversion from VV to VA ECMO.Results: Before ECMO, there was no difference between VV and VA ECMO patients in mean oxygenation index (83 v 83), mean airway pressure (18.4 v 18.9 cm H₂O), ECMO cannulation age (28 v 20 hours), or in the percentage of patients who needed dopamine and dobutamine (100% v 100%). From November 1994, nitric oxide (NO) was available; before ECMO, 11 of 14 (79%) VV ECMO patients received NO versus 9 of 10 (90%) patients in the VA group. VV ECMO patients were larger (3.34 v 2.77 kg; P < .05) and of advanced gestational age (39.0 v 36.9 wk; P < .05) compared with VA ECMO patients. There was no significant difference between VV and VA ECMO patients in survival rate (18 of 26, 69% v 13 of 19, 68%), ECMO duration (152 v 150 hours), time of extubation (32.0 v 33.5 days), age at discharge (73 v 81 days), or incidence of short-term intracranial complications (3.8% v 10.5%) or myocardial stun (3.8% v 15.8%).Conclusions: The authors conclude that VV ECMO is as reliable as VA ECMO in newborns with CDH in severe respiratory failure who need ECMO support and who can accommodate the VV double-lumen catheter. Because of its potential advantages, VV ECMO may be the preferred ECMO method in these infants.     

Extracorporeal membrane oxygenation in infants with meconium aspiration syndrome: a decade of experience with venovenous ECMO

Background

Despite the emergence of new therapies for respiratory failure of the newborn with meconium aspiration syndrome (MAS), extracorporeal membrane oxygenation (ECMO) has a significant role as a rescue modality in these infants. Our objective was to compare the use of venovenous (VV) vs venoarterial (VA) ECMO in newborns with MAS who need ECMO and to ascertain the impact of new therapies in these infants during the last decade. We also evaluated how disease severity or time of ECMO initiation affected mortality and morbidity.

Methods

A report of 12 years experience (1990-2002) of a single center, comparing VV and VA ECMO, is given. Venovenous ECMO was the preferred rescue modality for respiratory failure unresponsive to maximal medical therapy. Venoarterial ECMO was used only when the placement of a VV ECMO 14-F catheter was not possible; 128 patients met ECMO criteria, 114 were treated with VV ECMO, and 12 with VA ECMO. Two patients were converted from VV to VA ECMO.

Results

Venovenous and VA ECMO patients had comparable birth weight (mean ± SEM, 3.48 ± 0.05 vs 3.35 ± 0.15 kg) and gestational age (40.3 ± 0.1 vs 40.7 ± 0.3 weeks). Before ECMO, there was no difference between VV and VA ECMO patients in oxygenation index (60 ± 3 vs 63 ± 8), mean airway pressure (19.5 ± 0.4 vs 20.8 ± 1.5 cm H₂O), alveolar-arterial O₂ gradient (630 ± 2 vs 632 ± 4 torr), ECMO cannulation age (median [25th-75th percentiles], 23 [14-47] vs 26 [14-123] hours), or in the % of patients who needed vasopressors/inotropes (98% vs 100%). From November 1994, inhaled nitric oxide (NO) was available. Before VV ECMO, 67% of the patients received NO, 24% received surfactant, and 48% were treated with high-frequency ventilation (HFV). There was no significant difference between VV and VA ECMO patients in survival rate (94% vs 92%), ECMO duration (88 [64-116] vs 94 [55-130] hours), time of extubation (9 [7-11] vs 14 [9-15] days), age at discharge (23 [18-30] vs 27 [15-41] days), or incidence of short-term intracranial complications (5.3% vs 16.7%). For the total cohort of 126 infants, indices of disease severity (oxygenation index, alveolar-arterial O₂ gradient, mean airway pressure) did not correlate with outcome measures. Delay in ECMO initiation (>96 hours) was associated with prolonged mechanical ventilation and hospitalization (P < .01). New therapies (NO, HFV, surfactant) in the second part of the decade were associated with a longer ECMO duration (98 [80-131] vs 87 [60-116] hours; P < .05), no delay in ECMO initiation time (23 [10-40] vs 24 [14-52] hours), and no significant change in survival (97% vs 92.5%). No patient was treated with VA ECMO after 1994.

Conclusions

Venovenous ECMO is as reliable as VA ECMO in newborns with MAS in severe respiratory failure who need ECMO. Delay in ECMO initiation may result in prolonged mechanical ventilation and increased length of hospital stay. The emergence of new conventional therapies (NO, HFV, surfactant) and particularly increased experience enable sole use of VV ECMO with no significant change in survival in infants with MAS.     

Comparison of a New Miniaturized Extracorporeal Membrane Oxygenation System With Integrated Rotary Blood Pump to a Standard System in a Porcine Model of Acute Lung Injury

Extracorporeal membrane oxygenation (ECMO) is used for severe acute respiratory distress syndrome. However, available ECMO systems are large and not well designed for fast delivery, emergency implantation, and interhospital transfer. Therefore, a new miniaturized oxygenator with integrated rotary blood pump (ILIAS) was developed and compared with a standard ECMO system in a large animal model. Acute lung injury was induced with repeated pulmonary saline lavage in 14 pigs until PaO₂/FiO₂‐ratio was <100 mm Hg with a positive‐end‐expiratory‐pressure of 5 mbar. Pigs were assigned to the following three groups: group 1 (n = 4): control group with conventional ventilation; group 2 (n = 5): standard vv‐ECMO; group 3 (n = 5): vv‐ILIAS. Gas exchange, hemodynamics, hemolysis, and coagulation activation were examined over a period of 8 h. No device failed during the observation period. PaCO₂ decreased from 59.40 ± 4.14 mm Hg to 48.62 ± 4.50 mm Hg after 1 h in the ILIAS group compared with an improvement of PaCO2 from 48.86 ± 7.45 to 40.10 ± 6.02 in the conventional ECMO group (P = not significant [n.s.]). ARDS‐induced respiratory acidosis was controlled promptly with a pH of 7.2 ± 0.1 at baseline increasing to 7.4 ± 0.1 in both study groups after 60 min of ECMO support. Mean carbon dioxide transfer was comparable between the conventional ECMO and ILIAS (211.36 ± 78.39 mL/min vs. 219.99 ± 76.72 mL/min, P = n.s.). PaO₂/FiO₂ increased from 118.4 ± 15.5 mm Hg to 179.1 ± 72.4 mm Hg in the ILIAS group compared with an improvement of oxygenation from 107.1 ± 24.9 mm Hg to 179.0 ± 45.7 mm Hg in the standard ECMO group (P = n.s.). Mean oxygen transfer was calculated with 136.09 ± 30.25 mL/min for the ILIAS and 129.05 ± 36.28 mL/min for the standard ECMO. Hemodynamic instability or significant activation of the plasmatic coagulation was not observed. However, hemolysis was significantly higher in the ILIAS group compared with the conventional ECMO. As the ILIAS prototype provided excellent gas exchange with hemodynamic stability comparable with a standard ECMO system, we believe this study serves as a proof of concept. Further development and design modifications (optimized rotation speed and surface coating of rotor) are already done and another experiment is projected to reduce hemolysis and platelet consumption for clinical application.     

Gastric Yield Pressure and Gastric Yield Volume to Assess Anti-Reflux Barrier in a Porcine Model

ABSTRACT

Anti-reflux barrier (ARB) resistance may be useful to test new treatments for gastroesophageal reflux (GER). The ARB has been estimated by increasing gastric yield pressure (GYP) and gastric yield volume (GYV) in animal models but has not been validated. This study aimed to develop an experimental model suitable for assessing the ARB resistance to increasing intragastric pressure and volume and its reproducibility in a seven-day interval. Ten two-month-old female Large-White swine were studied. Intragastric pressure and volume were recorded using a digital system connected to a Foley catheter inserted through gastrostomy into the stomach. GYP and GYV were defined as the gastric pressure and volume able to yield gastric contents into the esophagus detected by esophageal pH. A sudden pH drop below 3 sustained during 5 min was considered diagnostic for gastric yield. Animals were studied again after seven days. On days 0 and 7, there were no significant differences for GYP (mean ± SD = 7.66 ± 3.02 mmHg vs. 7.07 ± 3.54 mmHg, p = .686) and GYV (636.70 ± 216.74 ml vs. 608.30 ± 276.66 ml; p = .299), respectively. Concordance correlation coefficient (ρ_c) was significant for GYP (ρ_c = 0.634, 95% CI = 0.141–0.829, p = .006), but not for GYV (ρ_c = 0.291, 95% CI = ?0.118 to 0.774, p = .196). This study demonstrated an experimental model, assessing the ARB resistance. GYP seems to be a more reliable parameter than GYV for assessment of ARB resistance.     

Non-assisted versus neuro-navigated and XperCT-guided external ventricular catheter placement: a comparative cadaver study

Background and purpose

Accurate placement of an external ventricular drain (EVD) for the treatment of hydrocephalus is of paramount importance for its functionality and in order to minimize morbidity and complications. The aim of this study was to compare two different drain insertion assistance tools with the traditional free-hand anatomical landmark method, and to measure efficacy, safety and precision.

Methods

Ten cadaver heads were prepared by opening large bone windows centered on Kocher’s points on both sides. Nineteen physicians, divided in two groups (trainees and board certified neurosurgeons) performed EVD insertions. The target for the ventricular drain tip was the ipsilateral foramen of Monro. Each participant inserted the external ventricular catheter in three different ways: 1) free-hand by anatomical landmarks, 2) neuronavigation-assisted (NN), and 3) XperCT-guided (XCT). The number of ventricular hits and dangerous trajectories; time to proceed; radiation exposure of patients and physicians; distance of the catheter tip to target and size of deviations projected in the orthogonal plans were measured and compared.

Results

Insertion using XCT increased the probability of ventricular puncture from 69.2 to 90.2 % (p?=?0.02). Non-assisted placements were significantly less precise (catheter tip to target distance 14.3?±?7.4 mm versus 9.6?±?7.2 mm, p?=?0.0003). The insertion time to proceed increased from 3.04?±?2.06 min. to 7.3?±?3.6 min. (p?<?0.001). The X-ray exposure for XCT was 32.23 mSv, but could be reduced to 13.9 mSv if patients were initially imaged in the hybrid-operating suite. No supplementary radiation exposure is needed for NN if patients are imaged according to a navigation protocol initially.

Conclusion

This ex vivo study demonstrates a significantly improved accuracy and safety using either NN or XCT-assisted methods. Therefore, efforts should be undertaken to implement these new technologies into daily clinical practice. However, the accuracy versus urgency of an EVD placement has to be balanced, as the image-guided insertion technique will implicate a longer preparation time due to a specific image acquisition and trajectory planning.     

Evaluation of mechanism of increased intracranial pressure with insufflation

Background: Previous studies have documented an increase in intracranial pressure with abdominal insufflation, but the mechanism has not been explained. Methods: Nine 30–35-kg domestic pigs underwent carbon dioxide insufflation at 1.5 l/min. Intracranial pressure (ICP), lumbar spinal pressure (LP), central venous pressure (CVP), inferior vena cava pressure (IVCP), heart rate, systemic arterial blood pressure, pulmonary arterial pressure, cardiac output, heart rate, respiratory rate, temperature, and end-tidal CO₂ were continuously measured. Mechanical ventilation was used to maintain a constant pCO₂. Measurements were recorded at 0, 5, 10, and 15 mmHg of abdominal pressure with animals in supine, Trendelenburg (T), and reverse Trendelenburg (RT) positions. Prior to recording measurements, the animals were allowed to stabilize for 40 min after each increase in abdominal pressure and for 20 min after each position change. Results: The animals showed a significant increase in ICP (mmHg) with each 5-mmHg increase in abdominal pressure (0 mmHg: 14 ± 1.7; 5 mmHg: 19.8 ± 2.3, p < 0.001; 10 mmHg: 24.8 ± 2.5, p < 0.001; 15 mmHg: 29.8 ± 4.7, p < 0.01). The ICP at 15 mmHg abdominal pressure increased further in the T position (39 ± 4, p < 0.01). Insufflating in the RT position did not significantly reduce the increase in ICP. The IVCP (mmHg) increased with increased abdominal pressure (0 mmHg: 11.5 ± 6.2, 15 mmHg: 22.1 ± 3.5, p < 0.01). This increase correlated with the increase in ICP and LP (r of mean pressures ≥0.95). There was no significant change in CVP. Conclusions: This study suggests that care may be needed with laparoscopy in patients at risk for increased ICP due to head injury or a space occupying lesion. The mechanism of increased ICP associated with insufflation is most likely impaired venous drainage of the lumbar venous plexus at increased intraabdominal pressure. Further studies of cerebral spinal fluid movement during insufflation are currently underway to confirm this hypothesis. Received: 28 March 1997/Accepted: 5 August 1997     

Evaluating quality of life of extracorporeal membrane oxygenation survivors using the pediatric quality of life inventory survey

Purpose

This study assesses the impact of extracorporeal membrane oxygenation (ECMO) associated morbidities on long-term quality of life (QOL) outcomes.

Effect of the Pulsatile Extracorporeal Membrane Oxygenation on Hemodynamic Energy and Systemic Microcirculation in a Piglet Model of Acute Cardiac Failure

The objective of this study was to compare the effects of pulsatile and nonpulsatile extracorporeal membrane oxygenation (ECMO) on hemodynamic energy and systemic microcirculation in an acute cardiac failure model in piglets. Fourteen piglets with a mean body weight of 6.08 ± 0.86 kg were divided into pulsatile (N = 7) and nonpulsatile (N = 7) ECMO groups. The experimental ECMO circuit consisted of a centrifugal pump, a membrane oxygenator, and a pneumatic pulsatile flow generator system developed in‐house. Nonpulsatile ECMO was initiated at a flow rate of 140 mL/kg/min for the first 30 min with normal heart beating, with rectal temperature maintained at 36°C. Ventricular fibrillation was then induced with a 3.5‐V alternating current to generate a cardiac dysfunction model. Using this model, we collected the data on pulsatile and nonpulsatile groups. The piglets were weaned off ECMO at the end of the experiment (180 min after ECMO was initiated). The animals did not receive blood transfusions, inotropic drugs, or vasoactive drugs. Blood samples were collected to measure hemoglobin, methemoglobin, blood gases, electrolytes, and lactic acid levels. Hemodynamic energy was calculated using the Shepard's energy equivalent pressure. Near‐infrared spectroscopy was used to monitor brain and kidney perfusion. The pulsatile ECMO group had a higher atrial pressure (systolic and mean), and significantly higher regional saturation at the brain level, than the nonpulsatile group (for both, P < 0.05). Additionally, the pulsatile ECMO group had higher methemoglobin levels within the normal range than the nonpulsatile group. Our study demonstrated that pulsatile ECMO produces significantly higher hemodynamic energy and improves systemic microcirculation, compared with nonpulsatile ECMO in acute cardiac failure.     

Chronic Changes of End-Systolic Pressure-Volume Relationship After Regional Myocardial Infarction

The chronic changes of the end-systolic pressure-volume relationship (ESPVR) after regional myocardial infarction were evaluated in a sheep model. Pressure-volume area (PVA) obtained from the pressure-volume diagram and left ventricular oxygen consumption (LVO₂) were studied. The regional myocardial infarction was created by ligating distal branches of the left coronary artery. ESPVR was obtained using a conductance catheter during transient inferior vena cava occlusion. Measurements were performed at baseline (n = 13), 1 hour (n = 8), 3 months (n = 9), and 6 months (n = 4) after infarction. Ees, the slope of the ESPVR did not change at 1 hour after infarction and remained the same at 3-month and 6-month measurements (baseline 2.26 ± 1.24 mmHg/mL, 1 hour 2.71 ± 1.06, 3 months 3.46 ± 1.51, 6 months 2.45 ± 0.64, NS). Because of the ventricular dilatation, which was demonstrated as an increase in changes of end-systolic volume (Ves) correlating with the time course after infarction (y = -3.21 + 0.128±, r = 0.454, p < 0.05), V₀, the volume intercept of the ESPVR increased at 1 hour after the infarction, and showed a tendency to increase at 3 months and 6 months after the infarction (baseline -18.0 ± 22.5 mL; 1 hour -0.9 ± 11.6; 3 months 5.4 ± 10.9, 6 months 9.2 ± 23.1, baseline vs 3 months p < 0.05, baseline vs 6 months p < 0.05). PVA and LVO₂ were unchanged over time after infarction (PVA: baseline 2097 ± 1526 mmHg/mL per 100 g^-1; 1 hour 1771 ± 699; 3 months 2483 ± 1086; 6 months 1,608 ±1,010, NS), (LVO₂: baseline 40.6 ± 13.1 ± 10–³ mL/100 g^-1 per beat^-1; 1 hour 42.9 ± 9.7; 3 months 35.0 ± 8.6; 6 months 31.2 ± 18.1, NS). Chronic regional infarction in the sheep model did not affect Ees over 6 months, but significantly increased V₀ after the increase in the acute phase. PVA and LVO₂ were not affected by this regional infarction either acutely or over 6 months.     

Use of Pentastarch Solution in the Treatment of Patients with Hemorrhagic Hypovolemia: Randomized Phase II Study in the Emergency Room

n = 12) or isotonic 0.9% NaCl solution (IS) ( n = 11), infused intravenously in 250-ml boluses, repeated until SBP > 100 mmHg. Blood pressure, infused volumes necessary to maintain SBP, and overall survival rates were determined and compared between groups. SBP increased significantly following either IS (from 64.4 ± 9.2 mmHg to 111.1 ± 6.3 mmHg), or PS (from 63.7 ± 10.6 mmHg to 108.1 ± 9.8 mmHg) when compared to admission values ( p < 0.05). Endovenous volumes infused were greater ( p = 0.001) in IS patients (1420 ± 298 ml) than in PS patients (356 ± 64 ml). No blood was transfused into PS patients, compared to 370 ± 140 ml of red blood cells transfused into IS patients ( p = 0.015). Mortality rates were similar in the two groups ( p = 0.725). We concluded that PS is a safe, efficient method for inducing hemodynamic recovery of hypovolemic trauma patients, with a clear reduction in the intravenous volumes required for acute resuscitation.     

Development of Hypertension in a Pyelonephritis-Induced Model: The Effect of Salt Intake and Inability of Renal Sodium Handling

The role of the kidney in the control of blood pressure has been convincingly demonstrated by several studies. Recent evidence has suggested that subtle acquired tubulointerstitial injury may cause a defect in sodium excretion function, thus leading to salt-sensitive hypertension. There are no reports, however, examining the effect of experimental chronic pyelonephritis on renal sodium handling and arterial pressure. Thus, to examine the influence of salt intake and unilateral nephrectomy, unanesthetized, unrestrained rats were randomly assigned to one of two separate groups: sham-operated rats (CO) or chronic unilateral pyelonephritic rats (CP). After twenty one days, the pyelonephritic group was subdivided in two: one subgroup continued with water intake (CPw), while the other was changed to 0.9% NaCl intake (CPs), like the control group (COs). After seven days, all rats were submitted to unilateral nephrectomy of the left normal kidney. Data presented herein show that chronic pyelonephritis produced an increase in mean arterial pressure (CO: 121.4 ± 1.0 mmHg to CP: 127.0 ± 0.9 mmHg, p = 0.000) that was enhanced by saline ingestion (COs: 121.6 ± 1.4 mmHg; CPw: 127.0 ± 1.8 mmHg; CPs: 132.1 ± 1.2 mmHg, p = 0.000) and further aggravated by unilateral nephrectomy (CO: 125.2 ± 2.6 mmHg; CPw: 127.5 ± 0.9 mmHg; CPs: 139.2 ± 1.1 mmHg, p = 0.000). Unchanged blood pressure measurements (120.2 ± 2.3 mmHg) were observed beyond 21 days in control rats maintained on water regimen when compared with saline-drinking groups. These changes in mean arterial pressure were observed despite an increased fractional sodium excretion in the CPs group compared to the other groups before uninephrectomy (COs: 0.125 ± 0.025%; CPw: 0.045 ± 0.013%; CPs: 0.292 ± 0.046%; p = 0.000), as compared to CPw after uninephrectomy (COs: 0.249 ± 0.077%; CPw: 0.062 ± 0.011%; CPs: 0.363 ± 0.195%, p = 0.019). In addition, it was shown that daily liquid intake was higher in CPs than in CPw but similar to COs, both before uninephrectomy (COs: 42.8 ± 2.6 ml/d; CPw: 34.3 ± 3.5 ml/d; CPs: 51.8 ± 3.7 ml/d, p = 0.006) and after uninephrectomy (COs: 40.9 ± 5.5 ml/d; CPw: 33.8 ± 1.4 ml/d; CPs: 53.0 ± 3.5 ml/d, p = 0.004). The current data suggest that chronic pyelonephritis promotes an inability of renal tubules to handle sodium excretion when exposed to sodium overload and aggravated by uninephrectomy, thus constituting a model for salt-sensitive hypertension.     

Continuous Renal Replacement Therapy Reduces the Systemic and Pulmonary Inflammation Induced by Venovenous Extracorporeal Membrane Oxygenation in a Porcine Model

Pulmonary changes in veno‐venous extracorporeal membrane oxygenation (VV‐ECMO) are rarely determined. We compared the contribution of VV‐ECMO and cannulation based on the observation of pulmonary inflammatory reaction and parenchymal construction in a porcine model of low tidal volume (V_T) ventilation. We also evaluated the effect of adding continuous renal replacement therapy (CRRT) to the ECMO circuit, because CRRT is known to reduce systemic cytokine release induced by VV‐ECMO. A total of 18 pigs undergoing low‐V_T ventilation were randomly divided into three groups (group 1, cannulation; group 2, VV‐ECMO; group 3, VV‐ECMO + CRRT) and studied for 24 h. Hemodynamic and ventilation parameters were recorded. We assessed plasma and alveolar cytokines, expression of pulmonary inflammatory genes, histopathological grading, and ultrastructural changes of the lungs. During the process, inspiratory volume increased and PaO₂ decreased in group 1. Systemic tumor necrosis factor‐α (TNF‐α) and interleukin 6 (IL‐6) levels increased at 2 h in group 2 and partly decreased in group 3. At 24 h, the levels of bronchoalveolar lavage fluid, TNF‐α, and IL‐6 in group 2 were remarkably higher than those in groups 1 and 3. Pulmonary mRNA expression of cytokines did not differ between the groups. We observed an increased score of pulmonary pathological findings in pro‐inflammatory cell infiltration and interstitial thickening of the lungs in group 2. The epithelium of the blood–air barrier after VV‐ECMO was swollen. In group 3, the pulmonary parenchyma and blood–air barrier were well preserved. We concluded that in a porcine model of low‐V_T ventilation, both VV‐ECMO and VV‐ECMO in combination with CRRT provided adequate oxygenation and carbon dioxide removal. Compared with VV‐ECMO alone, VV‐ECMO in combination with CRRT better preserved the lung parenchyma by eliminating systemic cytokines.     

Avalon catheters in pediatric patients requiring ECMO: Placement and migration problems

Purpose

The Avalon dual-lumen venovenous catheter has several advantages, but placement techniques and management have not been adequately addressed in the pediatric population. We assessed our institutional outcomes and complications using the Avalon catheter in children.

Brain tissue oxygen monitoring: a study of in vitro accuracy and stability of Neurovent-PTO and Licox sensors

Object

Periods of brain tissue ischemia are common after severe head injury, and their occurrence and duration are negatively correlated with outcome. Accurate and reliable measurement of brain tissue oxygenation (B_ti pO₂) may be a key to improve patient outcome after severe head injury. Knowledge of stability and accuracy of the B_ti pO₂ systems is crucial. We have therefore conducted a bench test study of new Neurovent-PTO® (NV) and Licox® (LX) oxygen tension catheters to evaluate the sensor accuracy, response time to different oxygen tensions, response to temperature changes and long-term stability.

Methods

For all experiments five new fluorescent NV sensors and five new electrochemical LX sensors were used. The catheter probes were placed into a container filled with a buffer solution. The solution was equilibrated with five high precision calibration gases. The accuracy of the probes was recorded after an equilibration period of 20 min in O₂ concentrations of 5, 10, 20, 30 and 40 mmHg at 37.0?±?0.2°C. The probe response to an increase in temperature from 37.0°C to 38.5°C to 40.0°C in two different gases with O₂ concentrations of 10 and 20 mmHg were analysed. We also recorded the time for reaching 90% of a new oxygen concentration level when switching from one concentration to another. Finally, to test if there was a time-dependant drift in pO₂ recordings, all sensors were left in 10 mmHg O₂ solution for 10 days, and recordings were taken every 24 h.

Results

In all gas concentrations, NV and LX sensors measured pO₂ with high accuracy and stability in vitro (mean differences from calculated values were for NV 0.76–1.6 mmHg and for LX ?0.46–0.26 mmHg). Both sensors showed a shorter response time to pO₂ increase (for NV 56?±?22 s and for LX 78?±?21 s) compared to pO₂ decrease (for NV 131?±?42 s and for LX 215?±?63 s). NV pO₂ values were more stable for changes in temperature, while LX sensors showed larger standard deviations with increasing temperature (the difference from the calculated values in 19.7 mmHg O₂ at 40°C were for NV probes between 0.5 and 1.7 mmHg and LX between ?2.3 and 1.9 mmHg). Both sensors gave stable results with low standard deviations during long-term (10 days) use, but with a slight elevation of measured pO₂ levels by time.

Conclusions

Both NV and LX were accurate in detecting different oxygen tensions, and they did not deviate over longer recording times. However, LX needed a significantly longer time to detect changes in pO₂ levels compared to NV. Furthermore, LX probes showed an increased standard deviation with higher temperatures.     

Effect of Nitric Oxide Synthase Inhibition and Saline Administration on Blood Pressure and Renal Sodium Handling During Experimental Sepsis in Rats

Much effort has been made in recent years to clarify metabolic and renal function changes in sepsis. A number of studies performed in different models of sepsis have been described. One such model that is frequently used is cecal ligation and puncture (CLP) in rats. This model resembles human sepsis in several important aspects, such as an early phase of hyperdynamic, hypermetabolic sepsis followed by a late hypodynamic, hypometabolic phase. The present study evaluated the blood pressure (n = 5) and renal function changes during development of CLP renal failure and to determine the effects of NOS inhibition (L-NAME) and 0.15 M NaCl administration on tail blood pressure and renal function in randomly assigned five groups (n = 10 each): (1) Sham-operated, (2) Sham-operated L-NAME-treated, (3) CLP rats, (4) CLP L-NAME-treated, and (5) CLP 0.15 M NaCl-treated rats. The basal tail blood pressure was not significantly different among the four groups. One week later, arterial pressure was significantly increased in sham-operated L-NAME-treated rats (159 ± 12 mmHg) compared with the other groups (118 ± 9.0 mmHg in nontreated rats, p<0.05). Blood pressure shows a slightly and not significant decrease up to 12 h in L-NAME and 0.15 M NaCl treated rats, which in turn was followed by a significant reduced arterial pressure 18 h after CLP in both groups (L-NAME: 96.0 ± 3.6 mmHg, p<0.05) and NaCl: 82.3 ± 2.4 mmHg, p<0.05) compared to sham-operated groups. The glomerular filtration rate estimated by C_Cr decreases significantly in the CLP untreated group (p<0.001) and did not significantly differ from the sham-operated and L-NAME-treated groups (p = 0.4) during the studies of renal tubule sodium handling. On the other hand, subcutaneous 0.15 M NaCl administration prevented C_Cr decreases in CLP rats (p = 0.25). CLP increased the FE_Na in the sham-operated from: 857.2 ± 85.1 Δ% min^?1 to CLP: 1197.8 ± 119.0 Δ% min^?1. The high FE_Na to CLP was blunted and significantly reduced by previous systemic treatment of animals with L-NAME from sham-operated + L-NAME: 1368.0 ± 72.0 Δ% min^?1 to CLP+L-NAME: 1148.0 ± 60.4 Δ% min^?1 (p<0.01). The enhanced FE_Na in the CLP group were accompanied by a significant increase in proximal sodium reabsorption rejection. The salient findings of the present study suggest that a decrease in the blood pressure and creatinine clearance caused by CLP may benefit from L-NAME and fluid resuscitation during initial bacteremia (first 12 h) by promoting an additional increase of tubule sodium reabsorption in the post-proximal segments of nephrons, but these therapies could not prevent acute renal failure after established endotoxemia.     

Outcome analysis of neonates with congenital diaphragmatic hernia treated with venovenous vs venoarterial extracorporeal membrane oxygenation

Purpose

Venoarterial extracorporeal membrane oxygenation (ECMO) (VA) is used more commonly in neonates with congenital diaphragmatic hernia (CDH) than venovenous ECMO (VV). We hypothesized that VV may result in comparable outcomes in infants with CDH requiring ECMO.

Methods

We retrospectively analyzed the Extracorporeal Life Support Organization (ELSO) database (1991-2006). Multivariate logistic regression analyses were used to compare VV- and VA-associated mortality.

Results

Four thousand one hundred fifteen neonates required ECMO, with an overall mortality rate of 49.6%. Venoarterial ECMO was used in 82% and VV in 18% of neonates. Pre-ECMO inotrope use and complications were equivalent between VA and VV. The mortality rate for VA and VV was 50% and 46%, respectively. After adjusting for birth weight, gestational age, prenatal diagnosis, ethnicity, Apgar scores, pH less than 7.20, Paco₂ greater than 50, requiring high-frequency ventilation, and year of ECMO, there was no difference in mortality between VV vs VA. Renal complications and on-ECMO inotrope use were more common with VV, whereas neurologic complications were more common with VA. The conversion rate from VV to VA was 18%; conversion was associated with a 56% mortality rate.

Conclusion

The short-term outcomes of VV and VA are comparable. Patients with CDH who fail VV may be predisposed to a worse outcome. Nevertheless, VV offers equal benefit to patients with CDH requiring ECMO while preserving the native carotid.     

Transintestinal oxygenation with perfluorocarbon

Objective: Perfluorocarbons are structurally similar to hydrocarbons but with the hydrogen atoms replaced by fluorine. In general, perfluorocarbons have an excellent oxygen and carbon dioxide carrying capacity. We studied the suitability of oxygenated perfluorocarbon as an agent for transintestinal oxygenation and measured its perfusion rates under different conditions. Subjects and Methods: We used FC-77 (Sumitomo 3M, Tokyo, Japan) perfluorocarbon and a rat hypoventilation model (room air, 20 breaths/min, a tidal volume of 10 ml/kg). Oxygenated FC-77 was perfused through the small intestine for 4 hours. Rats were allocated to 3 experimental groups according to the perfusion rate and a control group: Group 1 (n=6), 10 ml/min; Group 2 (n=6), 2.5 ml/min; Group 3 (n=6), 0.75 ml/min; Group 4 (n=6) served as a control (hypoventilation only). Arterial blood samples were drawn every 30 minutes. Standard blood gas analysis was performed. Results: After four hours of perfusion, the PaO2 levels in Groups 1 to 3 were significantly better than Group 4 (p<0.01, Group 1: 141.7+18.0 mmHg, Group 2: 145.2±25.1 mmHg, Group 3: 120.5±21.2 mmHg, Group 4: 67.4±7.2 mmHg). PaCO2 levels in Groups 1 and 2 were significantly better than Groups 3 and 4 (p<0.01, Group 1: 42.6±7.2 mmHg, Group 2: 52.1±7.7 mmHg, Group 3: 78.2±22.8 mmHg, Group 4: 75.3±10.3 mmHg). Conclusion: In the present settings, 8 ml/kg/min was adequate for oxygenation and CO ₂, clearance. This approach promises to become another modality for respiratory assistance.     

Hyperphosphatemia is prevalent among children with nephrotic syndrome and normal renal function

The aim of the study was to analyze systematically our observation that children with severe nephrotic syndrome (NS) have hyperphosphatemia despite normal kidney function. Forty-seven children with NS and normal glomerular filtration rate (GFR) were studied [26 with steroid-sensitive nephrotic syndrome (SSNS) and 21 with persistent NS]. The plasma phosphate level was expressed as the number of standard deviations (SDs) from the mean levels in age- and gender-matched controls. In SSNS plasma phosphate concentration was elevated (+3.7±2.0 SDs) during relapse and normalized (−0.7±1.7 SDs) in remission. In persistent NS the phosphate level was +4.0±2.1 SDs. Patients with marked hyperphosphatemia (>4 SDs) were younger (p<0.001), had lower plasma albumin (p<0.001), and had higher urinary protein levels (p<0.05). Hyperphosphatemia did not correlate with GFR, plasma calcium, or urinary sodium levels. Children with persistent NS had decreased serum 25(OH)D₃ and insulin-like growth factor 1 (IGF-1) concentrations. Hyperphosphatemia is prevalent among children with persistent nephrotic syndrome and normal renal function, correlates with its severity, and may result from increased urinary IGF-1 wasting.