Passive Leg Raising After Left Ventricular Assist Device Implantation.

Left ventricular assist device (LVAD) implantation is a common procedure in patients with end-stage heart failure. Although optimal fluid management is essential for acceptable postoperative treatment, it is critical to identify which patients will benefit from fluid administration. Passive leg raising (PLR) is a validated dynamic method that predicts fluid responsiveness in patients with heart failure by inducing a transient increase in cardiac preload. We performed a prospective study on 20 consecutive patients who underwent PLR maneuvers after LVAD implantation. Left ventricular assist device flow, end-tidal carbon dioxide, central venous pressure (CVP), and mean arterial pressure (MAP) were measured before and after PLR. Passive leg raising responsiveness was defined as at least a 15% increase in LVAD flow: (11 were responders and 9 nonresponders). Of the responders, 7 had right ventricular dysfunction (≥3). Passive leg raising responsiveness was associated with an increase of 19% in the LVAD flow, the mean CVP was raised from 11.3 to 14.4 mm Hg and the MAP from 82.6 to 86.7 mm Hg. After PLR, end-tidal carbon dioxide was increased by 4.6 mm Hg in the responders and 1.1 mm Hg in the nonresponders. The PLR maneuver is a noninvasive and easy to perform method that uses LVAD flow to assess fluid responsiveness in patients with heart failure after LVAD implantation.

Assessment of Left Ventricular Dimensions by Transoesophageal Echocardiography in Patients During Coronary Artery Bypass Surgery.

OBJECTIVE: Normative values of left ventricular (LV) end-diastolic area and diameter (EDA and EDD) for intraoperative transoesophageal echocardiography (TEE) have not been established. We aimed to define the ranges of LV EDA and EDD for intraoperative TEE examinations in patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: A MEDLINE search for studies reporting LV EDA and EDD in CABG patients was performed. Individual-level dataset from 333 anaesthetised and mechanically ventilated patients with preserved LV function (study population) were received from 8 studies. EDA and calculated EDD values in the study population were compared with summary mean EDD values obtained by transthoracic echocardiography (TTE) in 2 studies of 500 awake patients with coronary artery disease (CAD). Further, the influence of prespecified factors on EDD was evaluated through a multivariate regression model. RESULTS: LV EDA and EDD values measured by TEE in anaesthetised CABG patients were 16.7±4.7 cm2 and 4.6±0.6 cm, respectively. EDD values measured by TEE in anaesthetised patients were 10% to 13% less those measured by TTE in 2 studies of awake patients (p<0.001). Body surface area, age and fractional area change but not sex were factors that affected LV EDD. CONCLUSION: LV EDD values measured by intraoperative TEE in anaesthetised and mechanically ventilated CABG patients were 10% to 13% less than those measured by TTE in awake CAD patients. This finding indicates that independent normative values specific for intraoperative TEE should be established for guiding intraoperative clinical decisions.

Extrinsic compression of the left main coronary artery by a contained aortic annular rupture following trans-catheter aortic valve implantation.

We present a case of an 83-year-old female who suffered from annular rupture with contained hematoma immediately after trans-apical implantation of balloon-expandable Sapien valve. The patient developed acute cardiogenic shock which resulted from an extrinsic compression of the left main coronary artery. We report the successful management of this complication.

Aortic valve-sparing surgery in Marfan syndrome.

BACKGROUND: Patients with Marfan syndrome are referred for cardiac surgery due to root aneurysm with or without aortic valve regurgitation. Because these patients are young and frequently present with normal-appearing aortic cusps, valve sparing is often recommended. However, due to the genetic nature of the disease, the durability of such surgery remains uncertain. METHODS: Between February 2004 and June 2012, 100 patients in our department suffering from aortic aneurysm with aortic valve regurgitation underwent elective aortic valve-sparing surgery. Of them, 30 had Marfan syndrome, were significantly younger (30 +/- 13 vs. 53 +/- 16 years), and had a higher percentage of root aneurysm, compared with ascending aorta aneurysm in their non-Marfan counterparts. We evaluated the safety, durability, clinical and echocardiographic mid-term results of these patients. RESULTS: While no early deaths were reported in either group, there were a few major early complications in both groups. At follow-up (reaching 8 years with a mean of 34 +/- 26 months) there were no late deaths, and few major late complications in the Marfan group. Altogether, 96% and 78% of the patients were in New York Heart Association functional class I-II in the Marfan and non-Marfan groups respectively. None of the Marfan patients needed reoperation on the aortic valve. Freedom from recurrent aortic valve regurgitation > 3+ was 94% in the Marfan patients. CONCLUSIONS: Aortic valve-sparing surgery in Marfan symdrome patients is safe and yields good mid-term clinical outcomes.

Evaluation of the impact of a quality improvement program and intensivist-directed ICU team on mortality after cardiac surgery.

OBJECTIVE: Quality improvement is an important pursuit for critical care teams. DESIGN: The authors performed an observational cohort study with historic control. SETTING: Eight-bed cardiac surgery ICU in a tertiary university hospital. PARTICIPANTS: A total of 4,866 patients undergoing cardiac surgery over a 6-year period between January 2005 and December 2010. INTERVENTIONS: In this study, the influence of the introduction of a quality improvement program under the supervision of a newly appointed intensivist on patient outcomes after cardiac surgery was evaluated. Patients were further divided into three 2-year periods: Period I, 2005-2006, before appointment of an intensivist; Period II, 2007-2008, after appointment of an intensivist and initial introduction of a quality improvement program; and Period III, 2009-2010, after implementation of the program and introduction of Critical Care Information Systems. MEASUREMENTS AND MAIN RESULTS: There were 1,633, 1,690, and 1,543 patients in each period, respectively. There was no significant difference in the severity of patient illness between the groups. Unadjusted in-hospital mortality decreased from 6.37% (104 patients) in Period I to 4.32% (73 patients) and 3.3% (51 patients) in Periods II and III, respectively (p< 0.01). CONCLUSIONS: Appointment of an intensivist-directed team model and introduction of quality improvement interventions were associated with decreased mortality after cardiac surgery.

Heparin-free management of intra-aortic balloon pump after cardiac surgery.

BACKGROUND: Anticoagulation with heparin is recommended in patients with an intra-aortic balloon pump (IABP) to prevent thrombosis and embolization. However, anticoagulation increases the risk of bleeding, particularly in the early postoperative period after cardiac surgery. We investigated the safety of heparin-free management after IABP insertion in patients who underwent cardiac surgery. METHODS: We studied 203 consecutive patients who received perioperative IABP support between August 2004 and December 2011. All patients were managed without heparin and were followed for thrombotic and/or hemorrhagic complications. RESULTS: Patients were divided into two groups, according to time of IABP treatment following surgery. Group I, 81 patients (39.9%) were treated less than 24 hours following surgery and Group II, 122 patients (60.1%) were treated more than 24 hours following surgery. Vascular complications developed in seven patients (3.4%), two in Group I and five in Group II. Three patients had major and four had minor limb ischemia. There were no major bleeding complications, but minor bleeding complications were observed in eight patients (4.2%). CONCLUSION: In patients undergoing cardiac surgery with IABP support, the rate of thromboembolic complications was relatively low compared to historical controls. Heparin-free management may reduce the risk of hemorrhagic complications, with a low risk of thrombotic complications. Heparin should not be routinely used in patients requiring IABP after cardiac surgery.

[Chronic thromboembolic pulmonary hypertension: can successful thrombendarterectomy normalize exercise capacity and gas exchange?].

INTRODUCTION: Chronic thromboembolic pulmonary hypertension, a rare complication of pulmonary embolism is amenable to thrombendarterectomy (TEA) and when successful, improves exercise capacity and normalizes resting pulmonary arterial pressure. GOAL: To test if exercise capacity and exercise gas exchange are also normalized after successful TEA. METHODS: Over a period of 4 years, 5 patients underwent TEA at Sheba Medical Center. All experienced marked clinical improvement; their functional capacity (NYHA class) improved by 1-3 stages and resting pulmonary blood pressure normalized. One to 3 years after surgery each underwent a 6 minute walking test and incremental exercise to measure maximal oxygen uptake. RESULTS: It was found that following TEA, the 6 minute walking distance improved by 100-215 meters and more. Maximal oxygen uptake remained below normal in 4/5 cases and ranged 42-87% of predicted values. Hemoglobin oxygen saturation that was normal after TEA at rest, fell in all with exercise to 91-96%. Exercise gas exchange remained abnormal, consistent with residual pulmonary vascuLar disease. CONCLUSIONS: Thrombendarterectomy in chronic thromboembolic pulmonary hypertension caused marked clinical improvement and normalized resting pulmonary arterial pressures. Exercise capacity also improved but peak oxygen uptake remained below normal and exercise gas exchange remained abnormal. SUMMARY: Chronic thromboembolic pulmonary hypertension can be effectively treated. However, despite remarkable improvement, residual pulmonary vascular disease persists and is not relieved following successful operation.

The impact of hyperlactatemia on postoperative outcome after adult cardiac surgery.

PURPOSE: To evaluate the value of blood lactate value in predicting postoperative mortality (primary outcome), duration of ventilation, and length of stay in an intensive care unit (ICU) and hospital (secondary outcomes). METHODS: We performed a prospective observation study on 1,820 consecutive patients undergoing open heart surgery in a tertiary university medical center. Blood lactate levels were obtained from patients on admission to the cardiac surgical ICU and measured serially. RESULTS: All patients were divided into three groups according to their maximum blood lactate levels: group I (normolactatemia, lactate ≤2.2 mmol/l), 332 patients; group II (mild hyperlactatemia, lactate 2.2-4.1 mmol/l), 1,054 patients; and group III (severe hyperlactatemia, lactate ≥4.4 mmol/l), 434 patients. Maximum blood lactate levels ≥4.4 mmol/l during the first 10 h post admission were associated with prolonged ventilation time, longer ICU stay, and increased mortality (P < 0.001). CONCLUSIONS: Hyperlactatemia is common after cardiac surgery. Maximal lactate threshold ≥4.4 mmol/l in the first 10 h after operation accurately predicts postoperative mortality.

Mitochondrial function and tissue vitality: bench-to-bedside real-time optical monitoring system.

BACKGROUND: The involvement of mitochondria in pathological states, such as neurodegenerative diseases, sepsis, stroke, and cancer, are well documented. Monitoring of nicotinamide adenine dinucleotide (NADH) fluorescence in vivo as an intracellular oxygen indicator was established in 1950 to 1970 by Britton Chance and collaborators. We use a multiparametric monitoring system enabling assessment of tissue vitality. In order to use this technology in clinical practice, the commercial developed device, the CritiView (CRV), is tested in animal models as well as in patients. METHODS AND RESULTS: The new CRV enables the optical monitoring of four different parameters, representing the energy balance of various tissues in vivo. Mitochondrial NADH is measured by surface fluorometry/reflectometry. In addition, tissue microcirculatory blood flow, tissue reflectance and oxygenation are measured as well. The device is tested both in vitro and in vivo in a small animal model and in preliminary clinical trials in patients undergoing vascular or open heart surgery. In patients, the monitoring is started immediately after the insertion of a three-way Foley catheter (urine collection) to the patient and is stopped when the patient is discharged from the operating room. The results show that monitoring the urethral wall vitality provides information in correlation to the surgical procedure performed.

Modified thromboelastography evaluation of platelet dysfunction in patients undergoing coronary artery surgery.

OBJECTIVE: Anti-platelet therapy is associated with increased perioperative bleeding. Although current guidelines call for its caessation 5-10 days prior to cardiac surgery, this could constitute an increased risk of preoperative myocardial infarction. The optimal safe period from discontinuation of anti-platelet therapy to surgery is as yet unknown for the individual patient. We investigated whether preoperative thromboelastography (TEG) with platelet mapping could predict bleeding tendency in patients (on recent anti-platelet therapy) undergoing coronary artery bypass grafting (CABG). METHODS: We prospectively evaluated 59 patients on aspirin and clopidogrel therapy who underwent CABG. Of them, 25 patients received aspirin alone. TEG with platelet mapping was performed immediately prior to surgery in all 59 patients. RESULTS: During the first 24h post-surgery, 9/59 patients bled excessively (1216 + or - 310 ml in excessive bleeding vs 576 + or - 155 ml in non-bleeding patients). Of the patients bled excessively, eight received clopidogrel treatment prior to surgery. However, 26 of the remaining 34 patients receiving clopidogrel did not bleed significantly. Clopidogrel-induced platelet dysfunction diagnosed by platelet mapping discerned between patients who demonstrated excessive bleeding and those who did not (78% - sensitivity, 84% - specificity, p=0.004). Aspirin-induced platelet dysfunction did not reflect a bleeding tendency. Of all patients, 85% did not respond to a standard dose of clopidogrel, whereas 44% did not respond to aspirin. CONCLUSIONS: TEG with platelet mapping is able to predict excessive postoperative blood loss among patients who underwent CABG and recent anti-platelet therapy. The prevalence of non-responsiveness to anti-platelet therapy, including clopidogrel, is higher in patients undergoing coronary artery bypass grafting than in the general population. In this study, aspirin-induced platelet dysfunction did not influence postoperative blood loss.

Giant left atrium needed negative pressure ventilation.

Giant left atrium (GLA) is seen in a variety of cardiac conditions. The GLA is diagnosed by combining the patient's history, physical examination, and imaging techniques, along with a computed tomographic chest scan, echocardiogram, and barium swallow test. We recently operated on a severely symptomatic 71-year-old woman with GLA (135 mm x 192 mm). We were forced to anesthetize her with negative pressure ventilation before connecting to the cardiopulmonary bypass circuit. Her postoperative course and long-term follow-up were uneventful. The procedure for GLA reduction is safe, even in very high-risk patients. Negative pressure ventilation may be used successfully as a bridge to cardiopulmonary bypass in certain cases.

Quality of mitral valve repair: median sternotomy versus port-access approach.

OBJECTIVES: We sought to compare early and late clinical and echocardiographic outcomes of patients undergoing minimally invasive mitral valve repair by means of the port-access and median sternotomy approaches. METHODS: Between 2000 and 2009, 503 patients had mitral valve repair, of whom 143 underwent surgical intervention for isolated posterior leaflet pathology: 61 through port access and 82 through median sternotomy. The port-access group had better preoperative New York Heart Association functional class (P = .007) and a higher rate of elective cases (97% vs 87%, P = .037). Other preoperative characteristics were similar between the groups, including mitral valve pathology and repair techniques. RESULTS: Operative, bypass, and clamp times were significantly longer in the port-access group. Mean hospital stay was 5.3 +/- 2.5 days in the port-access group versus 5.7 +/- 2.5 days in the median sternotomy group (P = .4). Early postoperative echocardiographic analysis showed that most patients in both groups had none or trivial mitral regurgitation and none of the patients had greater than grade 2 mitral regurgitation. Follow-up extended for up to 100 months (mean, 34 +/- 24 months). New York Heart Association class improved in both groups (P = .394). Freedom from reoperation was 97% and 95% in the port-access and median sternotomy groups, respectively. Late echocardiographic analysis revealed that 82% (49/60) in the port-access group and 91% (73/80) in the median sternotomy group were free from moderate or severe mitral regurgitation (P = .11). CONCLUSIONS: In isolated posterior mitral valve pathology, quality of mitral valve repair with the port-access approach can compare with that with the conventional median sternotomy approach.

A randomized trial of outcomes of anesthetic management directed to very early extubation after cardiac surgery in children.

OBJECTIVES: Intraoperative management directed to early extubation of children undergoing cardiac surgery has been suggested as a viable alternative to prolonged postoperative mechanical ventilation. The authors evaluated the safety and efficacy of this approach in a randomized prospective trial. DESIGN: A prospective randomized observational study. SETTING: A single university-affiliated hospital. PARTICIPANTS: One hundred consecutive pediatric patients (age 1 month-15 years, weight 3.0-51 kg) requiring cardiac surgery. Patients younger than 1 month of age and those requiring mechanical ventilation before the operation were considered ineligible for the study. INTERVENTIONS: Patients were randomly allocated to a group with anesthetic management and extubation in the operating room (early group [EG]) and a group with elective prolonged mechanical ventilation (control group [CG]). MEASUREMENTS AND MAIN RESULTS: A difference in outcome as reflected by the pediatric intensive care unit (PICU) and hospital lengths of stay and postoperative morbidity and mortality was analyzed. A separate analysis was performed in children younger than 3 years old. The extubation time in the CG was 25.0 +/- 26.9 hours. No differences in mortality, the need for re-exploration for bleeding, the need for reintubation, the incidence of abnormal chest radiographic findings, or cardiac and septic complications between groups were found. PICU and postoperative hospital lengths of stay were significantly shorter in patients in the EG (3.3 +/- 1.9 days in the EG v 5.8 +/- 4.1 in the CG, p < 0.001, and 7.4 +/- 2.9 days in the EG v 11.2 +/- 6.8 days in the CG, p = 0.009). CONCLUSIONS: In children undergoing cardiac surgery, anesthetic management with early cessation of mechanical ventilation appears to be safe and decreases hospital and PICU length of stay. However, because the size of the study did not allow for the detection of possible differences in perioperative mortality, only a large multicenter study may provide a definite answer to this question. The present study may be treated as a pilot for such a trial.

Risk factors for failed "fast-tracking" after cardiac surgery in patients older than 70 years.

OBJECTIVE: "Fast-track" pathways have been successfully used in low-risk, relatively young patients after all types of surgical procedures including cardiac surgery. An increase in the number of referrals of older patients for cardiac surgery prompted the present study on the use of a "fast-track" pathway in septuagenarians and octogenarians. Risk factors for the unsuccessful application of the "fast-track" pathway in these elderly patients were determined. DESIGN: A retrospective observational study. SETTING: A single tertiary-care, university-affiliated center. PARTICIPANTS: All 70-year-old or older patients undergoing cardiac surgery between January 1, 2004 and June 30, 2007 were included. Septuagenarians were compared with octogenarians. MEASUREMENTS AND MAIN RESULTS: During the 42-month period, 860 cardiac operations were performed on 576 septuagenarians and 284 octogenarians. The "fast-track" pathway was successful in 54.5% and 37.3%, respectively. On multiple logistic regression analyses, stroke, renal failure, and procedures other than primary isolated coronary artery bypass graft surgery were independently associated with failed early extubation, delayed intensive care unit discharge, and delayed hospital discharge in both groups. Infections and atrial fibrillation were independent risk factors for delayed hospital discharge in both groups and delayed intensive care unit discharge in the octogenarians. In the octogenarians only, congestive heart failure was an independent risk factor for failed early extubation, delayed intensive care unit discharge, and delayed hospital discharge. CONCLUSIONS: A "fast-track" pathway may be applied in selected septuagenarians and octogenarians. Age alone should not exclude consideration for "fast-track" management.

Minimally invasive congenital cardiac surgery through right anterior minithoracotomy approach.

BACKGROUND: Median sternotomy has been the conventional approach for correction of congenital cardiac defects despite poor cosmetic results at times. Right anterior minithoracotomy was, therefore, assessed as an alternative procedure with a better cosmetic outcome. METHODS: From October 2002 through February 2007, 75 patients underwent correction of congenital cardiac malformations with the use of cardiopulmonary bypass through right anterior minithoracotomy involving a short incision through the fifth intercostal space and the minimally invasive cannulation. Of them, 18 patients were infants, 42 were children, and 15 were adult. The average age was 9.26 +/- 14.1 years (range, 1.2 to 56). The average weight was 19.59 +/- 24.3 kg (range, 8.5 to 118 kg). The corrected defects included atrial septal defect type II, sinus venosus atrial septal defect with partial anomalous pulmonary venous drainage, atrial component of atrioventricular septal defect, perimembranous ventricular septal defects with patent foramen ovale, mitral valve repair (complex), repair of cleft mitral valve, cor triatum atrial septal defect, repair of double-chambered right ventricle and extraction of atrial septal defect closure device. Skin incisions were as long as 5 cm. RESULTS: There was no operative or late mortality or major morbidity. The mean cardiopulmonary bypass time was 58.67 +/- 35.11 minutes (range, 32 to 263). Sixty-five patients were extubated in the operating room; the remaining 10 patients were extubated within 4 hours. Cosmetic result was very satisfactory in all patients. Two adult patients complained of some right chest musculoskeletal discomfort. CONCLUSIONS: The right anterior minithoracotomy incision is a safe and effective alternative to a median sternotomy for correction of congenital heart defects. Cosmetic results are highly satisfactory.

[Ventricular assist devices as bridge to heart transplantation in cardiogenic shock or terminal heart failure--12 years experience at the Sheba Medical Center].

BACKGROUND: Patients in cardiogenic shock (CS) or with terminal heart failure (THF) are at imminent risk of death while waiting for heart transplantation (HTx). Implantation of left or bi-ventricular assist device (LVAD/BiVAD) as a bridge to HTx may save many of these doomed patients' lives. PATIENTS AND METHODS: Between March 1994 and December 2006, 29 terminally ill patients (age 2.5-65 years, mean 48 years) underwent VADs implantation as bridge to HTx. The HeartMate VE LVAD was used in 18 patients, Thoratec pneumatic BiVAD in 7, Berlin Heart Excor BiVAD in one, and HeartMate II axial flow, Thoratec pneumatic and Biomedicus centrifugal LVADs in one each. Indications for VADs implantation were CS in 16 patients (55%) and intractable THF in 13 pts (45%). Etiologies were ischemic in 20 patients, idiopathic dilated, myocarditis and congenital in 2 patients each, and valvular, post partum and HTx graft vasculopathy in one patient each. RESULTS: Seventeen patients (59%) survived VADs implantation and underwent HTx or are ongoing. Mean survival on VADs was 72 days (range 1-353 days, total 5.2 patient years). Seven patients (24%) were discharged home while on LVAD support for a mean of 146 days. Nine of the transplanted patients (64%) were discharged home. In 4 LVAD patients the cause of death was RV failure necessitating later implantation of RVAD. CONCLUSIONS: VADs implantation as bridge to HTx in CS or THF saves many of these doomed patients, sometimes providing quality out-of-hospital life while waiting for HTx. Early recognition of RV failure and liberal use of BiVAD is important.

Anesthesia for port-access cardiac surgery in a pediatric population.

OBJECTIVE: A less invasive approach to cardiac surgical procedures has become widely accepted. The Port-Access (Heartport Inc, Redwood City, CA) technique for correction of acquired and congenital heart defects in adults produces superior cosmetic results without increasing perioperative morbidity. This study evaluated the feasibility of the Port-Access approach for repairs of various congenital heart defects in children and describes the anesthetic management for this procedure. DESIGN: Prospective observational study. SETTING: University hospital. PARTICIPANTS: Ten 3- to 15-year-old patients. INTERVENTIONS: Patients underwent repairs of congenital heart defects via minimal right thoracotomy. The induction and maintenance of anesthesia were tailored to achieve early extubation. Endotracheal intubation with a double-lumen tube was performed in 3 patients with body weight more than 25 kg. In other patients, lung separation was achieved with the use of a bronchial blocker. Arterial and venous cannulation were done under transesophageal echocardiography (TEE) guidance. A small surgical incision was performed in the fifth right intercostal space. In most patients, operations were performed on a fibrillating heart in normothermic condition. RESULTS: TEE-guided cannulation posed no technical difficulties. Flow rates, calculated for patients' body surface area, were easily achieved. No inotropic support was necessary for the separation from cardiopulmonary bypass. All patients but 1 were extubated in the operating room. Despite longer times of operation and cardiopulmonary bypass, intensive care unit stay and postoperative hospital length of stay were not different from the historic matched control group and were 2.7 +/- 1.1 days and 5.0 +/- 1.6 days, respectively. CONCLUSIONS: The Port-Access method for the correction of selected congenital cardiac defects is feasible in children.

Assessing fluid-responsiveness by a standardized ventilatory maneuver: the respiratory systolic variation test.

Respiratory-induced changes in arterial blood pressure predict fluid responsiveness. However, the accuracy of these variables is affected by the preset tidal volume and by the early inspiratory increase in arterial blood pressure. We have therefore calculated the slope produced by the minimal systolic blood pressures (plotted against the respective airway pressures) during a ventilatory maneuver consisting of four incremental, successive, pressure-controlled breaths, termed the Respiratory Systolic Variation Test (RSVT). In 14 ventilated patients, after major vascular surgery, the slope of the RSVT decreased significantly after intravascular fluid administration and correlated with the end-diastolic area and with changes in cardiac output better than filling pressures. This preliminary study suggests that a standardized ventilatory maneuver may be useful in guiding fluid therapy in ventilated patients.

Compression of the pulmonary artery during transesophageal echocardiography in a pediatric cardiac patient.

IMPLICATIONS: Hemodynamic compromise caused by the insertion of the probe for transesophageal echocardiography in a patient with severe stenosis of the main pulmonary artery is reported for the first time. The first symptom of the impending problem was a rapid decrease of end-tidal CO(2).