John H. Arnold

Two internal thoracic artery grafts are better than one

OBJECTIVE Does the use of bilateral internal thoracic artery (ITA) grafts provide incremental benefit relative to the use of a single ITA graft? METHODS We conducted a retrospective, nonrandomized, long-term (mean follow-up interval of 10 postoperative years) study of patients undergoing elective primary isolated coronary bypass surgery who received either single (8123 patients) or bilateral ITA grafts (2001 patients), with or without additional vein grafts. Multiple statistical methods including propensity score matching, and multivariable parsimonious and nonparsimonious risk factor analyses were used to address the issues of patient selection and heterogeneity. RESULTS In-hospital mortality was 0.7% for both the bilateral and single ITA groups. Survival for the bilateral ITA group was 94%, 84%, and 67%, and for the single ITA group 92%, 79%, and 64% at 5, 10, and 15 postoperative years, respectively (P <.001). Death, reoperation, and percutaneous transluminal coronary angioplasty were more frequent for patients undergoing single rather than bilateral ITA grafting, and this observation remained true despite multiple adjustments for patient selection, sampling, and length of follow-up. The differences between the bilateral and single ITA groups were greatest in regard to reoperation. The extent of benefit of bilateral ITA grafting varied according to patient-related variables, but no patient subsets were identified for whom single ITA grafting could be predicted to provide an advantage. CONCLUSIONS Patients who received 2 ITA grafts had decreased risks of death, reoperation, and angioplasty.

Durability of mitral valve repair for degenerative disease

BACKGROUND Degenerative mitral valve disease is the most common cause of mitral regurgitation in the United States. Mitral valve repair is applicable in the majority of these patients and has become the procedure of choice. OBJECTIVE This study was undertaken to identify factors influencing the durability of mitral valve repair. PATIENTS AND METHODS Between 1985 and 1997, 1072 patients underwent primary isolated mitral valve repair for valvular regurgitation caused by degenerative disease. Repair durability was assessed by multivariable risk factor analysis of reoperation. It was supplemented by a search for valve-related risk factors for death before reoperation. Three hospital deaths occurred (0.3%); complete follow-up (4152 patient-years) was available in 1062 of 1069 hospital survivors (99.3%). RESULTS At 10 years, freedom from reoperation was 93%. Among 30 patients who required reoperation for late mitral valve dysfunction, the repair failed in 16 (53%) as a result of progressive degenerative disease. Durability of repair was adversely affected by pathologic conditions other than posterior leaflet prolapse, use of chordal shortening, annuloplasty alone, and posterior leaflet resection without annuloplasty. Durability was greatest after quadrangular resection and annuloplasty for posterior leaflet prolapse and was enhanced by the use of intraoperative echocardiography. Death before reoperation was increased in patients having isolated anterior leaflet prolapse or valvular calcification and by use of chordal shortening or annuloplasty alone. CONCLUSIONS Repair durability is greatest in patients with isolated posterior leaflet prolapse who have posterior leaflet resection and annuloplasty. Chordal shortening, annuloplasty alone, and leaflet resection without annuloplasty jeopardize late results.

Prospective, randomized comparison of high-frequency oscillatory ventilation and conventional mechanical ventilation in pediatric respiratory failure

Objective: To compare the effectiveness of high‐frequency oscillatory ventilation with conventional mechanical ventilation in pediatric patients with respiratory failure. Setting: Five tertiary care pediatric intensive care units. Design: A prospective, randomized, clinical study with crossover. Patients: Seventy patients with either diffuse alveolar disease and/or airleak syndrome were randomized to receive high‐frequency oscillatory ventilation or conventional mechanical ventilation. Interventions: Patients randomized to receive high‐frequency oscillatory ventilation were managed, using a strategy that consisted of aggressive increases in mean airway pressure to attain the “ideal” lung volume and to achieve an arterial oxygen saturation of ≥90%, with an Fio2 of ≤0.6. Patients who were randomized to receive conventional mechanical ventilation were treated with a strategy that utilized increases in end‐expiratory pressure and inspiratory time to increase mean airway pressure and to limit increases in peak inspiratory pressure. Target blood gas values were the same for both groups. Crossover to the alternate ventilator was required if the patient met defined criteria for treatment failure. Measurements and Main Results: Physiologic data and ventilatory parameters were collected prospectively at predetermined intervals after randomization. Airleak Scores were derived daily, based on the chest radiograph and the patients clinical condition. In the high‐frequency oscillatory ventilation group, the Pao2/Pao2 ratio increased significantly and the oxygenation index (mean airway pressure × Fio2 × 100/Pao2) decreased significantly over time. There were no differences between the groups in duration of mechanical ventilation, frequency of airleak, Airleak Scores, or 30‐day survival rates. Significantly fewer patients treated with high‐frequency oscillatory ventilation required supplemental oxygenation at 30 days compared with patients managed with conventional ventilation. When ventilatory subgroups were compared, the patients managed with high‐frequency oscillation only had significantly better ranked outcomes than patients managed with conventional ventilation only. Conclusions: Our results indicate that high‐frequency oscillatory ventilation, utilizing an aggressive volume recruitment strategy, results in significant improvement in oxygenation compared with a conventional ventilatory strategy designed to limit increases in peak airway pressures. Furthermore, despite the use of higher mean airway pressures, the optimal lung volume strategy used in this study was associated with a lower frequency of barotrauma, as indicated by requirement for supplemental oxygen at 30 days, and improved outcome compared with conventional mechanical ventilation. (Crit Care Med 1994; 22:1530–1539)

GREIT: A unified approach to 2D linear EIT reconstruction of lung images

Electrical impedance tomography (EIT) is an attractive method for clinically monitoring patients during mechanical ventilation, because it can provide a non-invasive continuous image of pulmonary impedance which indicates the distribution of ventilation. However, most clinical and physiological research in lung EIT is done using older and proprietary algorithms; this is an obstacle to interpretation of EIT images because the reconstructed images are not well characterized. To address this issue, we develop a consensus linear reconstruction algorithm for lung EIT, called GREIT (Graz consensus Reconstruction algorithm for EIT). This paper describes the unified approach to linear image reconstruction developed for GREIT. The framework for the linear reconstruction algorithm consists of (1) detailed finite element models of a representative adult and neonatal thorax, (2) consensus on the performance figures of merit for EIT image reconstruction and (3) a systematic approach to optimize a linear reconstruction matrix to desired performance measures. Consensus figures of merit, in order of importance, are (a) uniform amplitude response, (b) small and uniform position error, (c) small ringing artefacts, (d) uniform resolution, (e) limited shape deformation and (f) high resolution. Such figures of merit must be attained while maintaining small noise amplification and small sensitivity to electrode and boundary movement. This approach represents the consensus of a large and representative group of experts in EIT algorithm design and clinical applications for pulmonary monitoring. All software and data to implement and test the algorithm have been made available under an open source license which allows free research and commercial use.

Tolerance and Dependence in Neonates Sedated with Fentanyl during Extracorporeal Membrane Oxygenation

We undertook a retrospective chart review of 37 neonates who received fentanyl by continuous infusion while undergoing extracorporeal membrane oxygenation (ECMO) between May 1986 and October 1988. We quantified the doses of all sedatives utilized, determined the incidence of neonatal abstinence syndrome (NAS), and identified risk factors associated with NAS. We determined peak fentanyl infusion rate, mean fentanyl infusion rate, total fentanyl dose, and duration of ECMO therapy. NAS was observed in 21 of 37 neonates (57%). In both the NAS and non-NAS neonates, mean infusion rate increased steadily during ECMO therapy, from a mean of 11.6 +/- 6.9 (SD) micrograms.kg-1.h-1 on day 1 to a mean of 52.5 +/- 19.4 (SD) micrograms.kg-1.h-1 by day 8. Total fentanyl dose and duration of ECMO were significantly greater in neonates with NAS. We found that neonates with a total dose greater than 1.6 mg/kg or an ECMO duration greater than 5 days had a significantly greater incidence of NAS (chi-squared test, P less than 0.01 and P less than 0.005; odds ratios = 7.0 and 13.9, respectively). With multiple logistic regression, ECMO duration was found to be the most powerful predictor of the occurrence of NAS. We also measured plasma fentanyl concentrations in a separate group of 5 neonates receiving fentanyl by continuous infusion for sedation. Fentanyl concentrations increased steadily during the period of infusion, suggesting the development of tolerance to the sedating effects. We conclude that continuous administration of fentanyl for sedation is associated with the uniform development of tolerance and a significant incidence of dependence. Alternative approaches to sedation should be investigated.

Inhaled nitric oxide in the treatment of postoperative graft dysfunction after lung transplantation

Pulmonary hypertension and transient graft dysfunction may complicate the postoperative course of patients undergoing lung transplantation. We report the acute effect of inhaled nitric oxide (80 ppm) on hemodynamics and gas exchange in 6 patients (median age, 14 years; range, 5 to 21 years) after lung transplantation as well as the effect of extended treatment over 40 to 69 hours in 2 patients. In 5 patients with pulmonary hypertension nitric oxide lowered mean pulmonary artery pressure (from 38.4 +/- 1.6 to 29.4 +/- 3.1 mm Hg; p < 0.05), pulmonary vascular resistance index (from 9.3 +/- 1.4 to 6.4 +/- 1.3 Um2; p < 0.05), and intrapulmonary shunt fraction (from 28.6% +/- 8.3% to 21.0% +/- 5.7%; p < 0.05). There was a 28.4% +/- 7.2% reduction in transpulmonary pressure gradient with only minor accompanying effects on the systemic circulation. Mean arterial pressure decreased only 2.7% +/- 5% (from 76.4 +/- 2.2 to 74 +/- 2.3 mm Hg; p = not significant), and systemic vascular resistance index by 4.2% +/- 9.7% (from 21.7 +/- 3.1 to 20.6 +/- 3.6 Um2; p = not significant). Cardiac index was unchanged (from 3.5 +/- 0.8 to 3.6 +/- 0.7 L.min-1.m-2; p = not significant). Nitric oxide caused a sustained improvement in oxygenation and pulmonary artery pressure during extended therapy at doses of 10 ppm. There were no major side effects. However, transient methemoglobinemia (9%) developed in 1 patient after 10 hours of nitric oxide treatment. Nitric oxide may be useful in the treatment of pulmonary hypertension and the impaired gas exchange that occurs after lung transplantation.

Aortic valve replacement: Is valve size important?

OBJECTIVE We sought to determine whether aortic prosthesis size adversely influences survival after aortic valve replacement. METHODS A total of 892 adults receiving a mechanical (n = 346), pericardial (n = 463), or allograft (n = 83) valve for aortic stenosis were observed for up to 20 years (mean, 5.0 +/- 3.9 years) after primary isolated aortic valve replacement. We used multivariable propensity scores to adjust for valve selection factors, multivariable hazard function analyses to identify risk factors for all-cause mortality, and bootstrap resampling to quantify the reliability of the results. RESULTS Twenty-five percent of patients had indexed internal orifice areas of less than 1.5 cm(2)/m(2) and more than 2 SDs (Z-value) below predicted normal aortic valve size. Mechanical valve orifices were smaller (1.3 +/- 0. 29 cm(2)/m(2), Z = -2.2 +/- 1.16) than pericardial (1.9 +/- 0.36 cm(2)/m(2), Z = -0.40 +/- 1.01) or allograft valves (2.1 +/- 0.50, Z = 0.24 +/- 1.17). The overall survival was 98%, 96%, 86%, 69%, and 49% at 30 days and 1, 5, 10, and 15 years postoperatively. Univariably, survival was weakly and inversely related to manufacturer valve size (P =.16) and internal orifice diameter (P =. 2) but completely unrelated to indexed valve area (P =.6) or Z-value (P =.8). These, and univariable differences among valve types (P =. 004), were accounted for by different prevalences in patient risk factors and not by valve size or type per se. Bootstrap resampling indicated that these findings had a less than 15% chance of being incorrect. CONCLUSIONS Survival after aortic valve replacement is strongly related to patient risk factors but appears not to be adversely affected by moderate patient-prosthesis mismatch (down to about 4 SDs below normal). Aortic root enlargement to accommodate a large prosthesis may be required in few situations.

State Behavioral Scale: a sedation assessment instrument for infants and young children supported on mechanical ventilation.

Objective: To develop and test the reliability and validity of the State Behavioral Scale for use in describing sedation/agitation levels in young intubated patients supported on mechanical ventilation. Design: In this prospective, psychometric evaluation, pairs of trained pediatric critical care nurse evaluators simultaneously and independently assessed a convenience sample of pediatric intensive care unit patients along eight state/behavioral dimensions and a numeric rating scale (NRS) of 0 (extremely sedated) to 10 (extremely agitated). The eight dimensions were derived from the sedation/agitation literature and expert opinion and included respiratory drive, response to ventilation, coughing, best response to stimulation, attentiveness to careprovider, tolerance to care, consolability, and movement after consoled, each with 3–5 levels. Setting: An 18-bed pediatric medical–surgical intensive care unit and 26-bed pediatric cardiovascular intensive care unit in a university-affiliated academic children’s hospital. Patients: A total of 91 intubated mechanically ventilated patients 6 wks to 6 yrs of age provided a median of two observations (interquartile range, 1–3) for a total of 198 sets of observations. Excluded were postoperative patients or those receiving neuromuscular blockade. Interventions: Patients were observed for 1 min, and then incremental levels of stimulation were applied until patient response. After 2 mins of consoling, the state behavioral assessment and NRS were completed. Measurements: Weighted kappa and intraclass coefficients were generated to assess interrater reliability of the eight dimension and NRS ratings. Distinct state behavior profiles were empirically identified from the dimension ratings using hierarchical cluster analysis using a squared Euclidean distance measure and between-groups linkage. Construct validity of these profiles was assessed by comparing group mean NRS scores using one-way analysis of variance. Main Results: Weighted kappa scores for all 198 dimension ratings ranged from .44 to .76, indicating moderate to good interrater reliability. The intraclass coefficient of .79 was high for NRS ratings. Cluster analysis revealed five distinct state profiles, with mean NRS ratings of 1.1, 2.5, 4.0, 5.3, and 7.6, all of which differed significantly from each other (F = 75.8, p < .001), supporting the profiles’ construct validity. Conclusions: Based on empirically derived state behavior profiles, we have constructed the State Behavioral Scale to allow systematic description of the sedation–agitation continuum in young pediatric patients supported on mechanical ventilation. Further studies including prospective validation and describing the effect of State Behavioral Scale implementation on clinical outcomes, including the quality of sedation and length of mechanical ventilation, are warranted.

High-frequency oscillatory ventilation in pediatric respiratory failure: A multicenter experience

ObjectiveThe use of high-frequency oscillatory ventilation (HFOV) has increased dramatically in the management of respiratory failure in pediatric patients. We surveyed ten pediatric centers that frequently use high-frequency oscillation to describe current clinical practice and to examine factors related to improved outcomes. DesignRetrospective, observational questionnaire study. SettingTen tertiary care pediatric intensive care units. PatientsTwo hundred ninety patients managed with HFOV between January 1997 and June 1998. InterventionsNone. Measurements and Main ResultsPatients were classified according to presence or absence of preexisting lung disease, symptomatic respiratory syncytial virus infection, or presence of cyanotic heart disease or residual right-to-left intracardiac shunt. In addition, patients for whom HFOV acutely failed were analyzed separately. Those patients with preexisting lung disease were significantly smaller, had a significantly higher incidence of pulmonary infection as the triggering etiology, and had a significantly greater duration of conventional ventilation before institution of HFOV compared with patients without preexisting lung disease. Stepwise logistic regression was used to predict mortality and the occurrence of chronic lung disease in survivors. In patients without preexisting lung disease, the model predicted a 70% probability of death when the oxygenation index (OI) after 24 hrs was 28 in the immunocompromised patients and 64 in the patients without immunocompromise. In the immunocompromised patients, the model predicted a 90% probability of death when the OI after 24 hrs was 58. In survivors without preexisting lung disease, the model predicted a 70% probability of developing chronic lung disease when the OI at 24 hrs was 31 in the patients with sepsis syndrome and 50 in the patients without sepsis syndrome. In the patients with sepsis syndrome, the model predicted a 90% probability of developing chronic lung disease when the OI at 24 hrs was 45. ConclusionsGiven the number of centers involved and the size of the database, we feel that our results broadly reflect current practice in the use of HFOV in pediatric patients. These results may help in deciding which patients are most likely to benefit from aggressive intervention by using extracorporeal techniques and may help identify high-risk populations appropriate for prospective study of innovative modes of supporting gas exchange (e.g., partial liquid breathing or intratracheal pulmonary ventilation).

Changes in the pharmacodynamic response to fentanyl in neonates during continuous infusion

Tolerance to opioid-induced sedation has been reported in neonates sedated with fentanyl by continuous infusion while undergoing extracorporeal membrane oxygenation. We undertook a prospective analysis of eight newborn infants sedated with fentanyl during extracorporeal membrane oxygenation therapy for respiratory failure. We recorded daily mean fentanyl infusion rate, measured serial plasma fentanyl concentrations, and documented the occurrence of spontaneous motor activity or respiratory effort. Mean fentanyl infusion rate increased steadily during the period of infusion from a mean of 9.2 +/- 1.9 (SEM) micrograms/kg per hour on day 1 to a mean of 21.9 +/- 4.5 micrograms/kg per hour by day 6. Mean plasma fentanyl concentrations increased steadily during the period of fentanyl infusion from 3.1 +/- 1.1 (SEM) ng/ml on day 1 to 13.9 +/- 3.2 ng/ml on day 6. All infants exhibited movement in response to gentle tactile stimulation throughout the period of infusion, and seven of eight infants manifested spontaneous movement of the extremities and eye opening. Our results indicate that when fentanyl is used for sedation in neonates, the plasma concentrations required for satisfactory sedation steadily escalate, possibly indicating the rapid development of tolerance to the sedating effects of fentanyl.