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1.  Hypercapnia Improves Tissue Oxygenation in Morbidly Obese Surgical Patients 
Anesthesia and analgesia  2006;103(3):677-681.
Risk of wound infection is increased in morbidly obese surgical patients, in part because a major determinant of wound infection risk, tissue oxygenation, is marginal. Unlike in lean patients, supplemental inspired oxygen (FIO2) only slightly improves tissue oxygenation in obese patients. Mild hypercapnia improves tissue oxygenation in lean, but has not been evaluated in obese patients. We thus tested the hypothesis that mild hypercapnia markedly improves tissue oxygenation in morbidly obese patients given FIO2 80% during major abdominal surgery. Thirty obese patients (body mass index 61.5±17 kg/m2) scheduled for open gastric bypass were randomly assigned to normocapnia (n=15, end-tidal PCO2 35 mmHg) or hypercapnia (n=15, end-tidal PCO2 50 mmHg); FIO2 was 80%. Anesthetic management and other confounding factors were controlled. Tissue oxygen tension was measured subcutaneously at the upper arm using a polarographic probe in a silastic tonometer. Demographic characteristics, cardiovascular measurements, and PaO2 (222±48 versus 230±68 mmHg in normocapnic versus hypercapnic; mean±SD, P=0.705) were comparable in the groups. Tissue oxygen tension, however, was greater in hypercapnic than in normocapnic patients (78±31 versus 56±13 mmHg, P=0.029). Mild hypercapnia increased tissue oxygenation by an amount believed to be clinically important and could potentially reduce the risk of surgical wound infection in morbidly obese patients.
PMCID: PMC1555622  PMID: 16931680
obesity; hypercapnia; tissue oxygenation; and wound infection
2.  Cardiorespiratory effects of protamine after cardiopulmonary bypass in man 
Thorax  1974;29(5):534-538.
Jastrzebski, J., Sykes, M. K., and Woods, D. G. (1974).Thorax, 29, 534-538. Cardiorespiratory effects of protamine after cardiopulmonary bypass in man. The cardiorespiratory changes following the injection of protamine sulphate (6 mg/kg) were studied in 15 patients who had undergone cardiopulmonary bypass. There was a transient fall in arterial pressure and a more prolonged increase in pulmonary artery pressure. There was a significant fall in arterial oxygen tension which was mainly due to a reduction in mixed venous oxygen tension resulting from a fall in cardiac output. Dead space/tidal volume ratio and percentage shunt did not change significantly.
PMCID: PMC470194  PMID: 4428453
3.  Cardiopulmonary effects of hypercapnia during controlled intermittent positive pressure ventilation in the horse. 
The cardiopulmonary effects of eucapnia (arterial CO2 tension [PaCO2] 40.4 +/- 2.9 mm Hg, mean +/- SD), mild hypercapnia (PaCO2, 59.1 +/- 3.5 mm Hg), moderate hypercapnia (PaCO2, 82.6 +/- 4.9 mm Hg), and severe hypercapnia (PaCO2, 110.3 +/- 12.2 mm Hg) were studied in 8 horses during isoflurane anesthesia with volume controlled intermittent positive pressure ventilation (IPPV) and neuromuscular blockade. The sequence of changes in PaCO2 was randomized. Mild hypercapnia produced bradycardia resulting in a significant (P < 0.05) decrease in cardiac index (CI) and oxygen delivery (DO2), while hemoglobin concentration (Hb), the hematocrit (Hct), systolic blood pressure (SBP), mean blood pressure (MBP), systemic vascular resistance (SVR), and venous admixture (QS/QT) increased significantly. Moderate hypercapnia resulted in a significant rise in CI, stroke index (SI), SBP, MBP, mean pulmonary artery pressure (PAP), Hct, Hb, arterial oxygen content (CaO2), mixed venous oxygen content (CvO2), and DO2, with heart rate (HR) staying below eucapnic levels. Severe hypercapnia resulted in a marked rise in HR, CI, SI, SBP, PAP, Hct, Hb, CaO2, CvO2, and DO2. Systemic vascular resistance was significantly decreased, while MBP levels were not different from those during moderate hypercapnia. No cardiac arrhythmias were recorded with any of the ranges of PaCO2. Norepinephrine levels increased progressively with each increase in PaCO2, whereas plasma cortisol levels remained unchanged. It was concluded that hypercapnia in isoflurane-anesthetized horses elicits a biphasic cardiopulmonary response, with mild hypercapnia producing a fall in CI and DO2 despite an increase in MBP, while moderate and severe hypercapnia produce an augmentation of the cardiopulmonary performance and DO2.
PMCID: PMC1263768  PMID: 8521355
4.  Temporary Diabetes Insipidus in 2 Men after On-Pump Coronary Artery Bypass Grafting 
Texas Heart Institute Journal  2013;40(1):99-101.
Many complications have been reported after cardiopulmonary bypass. A common physiologic change during the early postoperative period after cardiopulmonary bypass is increased diuresis. In patients whose urine output is increased, postoperative diabetes insipidus can develop, although reports of this are rare. We present the cases of 2 patients who underwent on-pump coronary artery bypass grafting (with cardiopulmonary bypass). Each was diagnosed with diabetes insipidus postoperatively: a 54-year-old man on the 3rd day, and a 66-year-old man on the 4th day. Each patient recovered from the condition after 6 hours of intranasal therapy with synthetic vasopressin (antidiuretic hormone). The diagnosis of diabetes insipidus should be considered in patients who produce excessive urine early after cardiac surgery in which cardiopulmonary bypass has been used.
PMCID: PMC3568285  PMID: 23466483
Cardiopulmonary bypass/adverse effects; coronary artery bypass; diabetes insipidus/diagnosis/drug therapy/etiology; diuresis; natriuretic agents/blood; postoperative complications/diagnosis/drug therapy/etiology; time factors; treatment outcome; vasopressin/therapeutic use
5.  Hyperlactatemia during cardiopulmonary bypass: determinants and impact on postoperative outcome 
Critical Care  2006;10(6):R167.
Hyperlactatemia during cardiopulmonary bypass is relatively frequent and is associated with an increased postoperative morbidity. The aim of this study was to determine which perfusion-related factors may be responsible for hyperlactatemia, with specific respect to hemodilution and oxygen delivery, and to verify the clinical impact of hyperlactatemia during cardiopulmonary bypass in terms of postoperative morbidity and mortality rate.
Five hundred consecutive patients undergoing cardiac surgery with cardiopulmonary bypass were admitted to this prospective observational study. During cardiopulmonary bypass, serial arterial blood gas analyses with blood lactate and glucose determinations were obtained. Hyperlactatemia was defined as a peak arterial blood lactate concentration exceeding 3 mmol/l. Pre- and intraoperative factors were tested for independent association with the peak arterial lactate concentration and hyperlactatemia. The postoperative outcome of patients with or without hyperlactatemia was compared.
Factors independently associated with hyperlactatemia were the preoperative serum creatinine value, the presence of active endocarditis, the cardiopulmonary bypass duration, the lowest oxygen delivery during cardiopulmonary bypass, and the peak blood glucose level. Once corrected for other explanatory variables, hyperlactatemia during cardiopulmonary bypass remained significantly associated with an increased morbidity, related mainly to a postoperative low cardiac output syndrome, but not to mortality.
Hyperlactatemia during cardiopulmonary bypass appears to be related mainly to a condition of insufficient oxygen delivery (type A hyperlactatemia). During cardiopulmonary bypass, a careful coupling of pump flow and arterial oxygen content therefore seems mandatory to guarantee a sufficient oxygen supply to the peripheral tissues.
PMCID: PMC1794481  PMID: 17134504
6.  Bench-to-bedside review: Permissive hypercapnia 
Critical Care  2004;9(1):51-59.
Current protective lung ventilation strategies commonly involve hypercapnia. This approach has resulted in an increase in the clinical acceptability of elevated carbon dioxide tension, with hypoventilation and hypercapnia 'permitted' in order to avoid the deleterious effects of high lung stretch. Advances in our understanding of the biology of hypercapnia have prompted consideration of the potential for hypercapnia to play an active role in the pathogenesis of inflammation and tissue injury. In fact, hypercapnia may protect against lung and systemic organ injury independently of ventilator strategy. However, there are no clinical data evaluating the direct effects of hypercapnia per se in acute lung injury. This article reviews the current clinical status of permissive hypercapnia, discusses insights gained to date from basic scientific studies of hypercapnia and acidosis, identifies key unresolved concerns regarding hypercapnia, and considers the potential clinical implications for the management of patients with acute lung injury.
PMCID: PMC1065087  PMID: 15693984
acidosis; acute lung injury; acute respiratory distress syndrome; buffering; hypercapnia; mechanical ventilation; ventilation induced lung injury; sepsis
7.  Assessment of tissue oxygen tension: comparison of dynamic fluorescence quenching and polarographic electrode technique 
Critical Care  2002;6(1):76-80.
Introduction and methods
Dynamic fluorescence quenching is a technique that may overcome some of the limitations associated with measurement of tissue partial oxygen tension (PO2). We compared this technique with a polarographic Eppendorf needle electrode method using a saline tonometer in which the PO2 could be controlled. We also tested the fluorescence quenching system in a rodent model of skeletal muscle ischemiahypoxia.
Both systems measured PO2 accurately in the tonometer, and there was excellent correlation between them (r2 = 0.99). The polarographic system exhibited proportional bias that was not evident with the fluorescence method. In vivo, the fluorescence quenching technique provided a readily recordable signal that varied as expected.
Measurement of tissue PO2 using fluorescence quenching is at least as accurate as measurement using the Eppendorf needle electrode in vitro, and may prove useful in vivo for assessment of tissue oxygenation.
PMCID: PMC83850  PMID: 11940270
clinical measurement methodology; fiberoptic measurement; fluorescence quenching; ischemia; Stern–Volmer; tissue oxygenation
8.  Supplemental Oxygen and Carbon Dioxide Each Increase Subcutaneous and Intestinal Intramural Oxygenation 
Anesthesia and analgesia  2004;99(1):207-211.
Oxidative killing by neutrophils, a primary defense against surgical pathogens, is directly related to tissue oxygenation. We tested the hypothesis that supplemental inspired oxygen or mild hypercapnia (end-tidal PCO2 of 50 mmHg) improves intestinal oxygenation. Pigs (25±2.5 kg) were used in two studies in random order: 1) Oxygen Study — 30% vs. 100% inspired oxygen concentration at an end-tidal PCO2 of 40 mmHg, and 2) Carbon Dioxide Study — end-tidal PCO2 of 30 mmHg vs. 50 mmHg with 30% oxygen. Within each study, treatment order was randomized. Treatments were maintained for 1.5 hours; measurements were averaged over the final hour. A tonometer inserted in the subcutaneous tissue of the left upper foreleg measured subcutaneous oxygen tension. Tonometers inserted into the intestinal wall measured intestinal intramural oxygen tension from the small and large intestines. 100% oxygen administration doubled subcutaneous oxygen partial pressure (PO2) (57±10 to 107±48 mmHg, P=0.006) and large intestine intramural PO2 (53±14 to 118±72 mmHg, P=0.014); intramural PO2increased 40% in the small intestine (37±10 to 52±25 mmHg, P=0.004). An end-tidal PCO2 of 50 mmHg increased large intestinal PO2 approximately 16% (49±10 to 57±12 mmHg, P=0.039), while intramural PO2 increased by 45% in the small intestine (31±12 to 44±16 mmHg, P=0.002). Supplemental oxygen and mild hypercapnia each increased subcutaneous and intramural tissue PO2, with supplemental oxygen being most effective.
PMCID: PMC1360187  PMID: 15281531
Oxygen: Intramural, Subcutaneous Intestinal; Ventilation: Increased Oxygen, Carbon Dioxide
9.  A marked increase in gastric fluid volume during cardiopulmonary bypass 
Major physiological stress occurs during cardiac surgery with cardiopulmonary bypass. This is related to hypothermia and artificial organ perfusion. Thus, serious gastrointestinal complications, particularly upper gastrointestinal bleeding, sometimes follow cardiac surgery. We have compared the antisecretory effects of a preanesthetic H2 antagonist (roxatidine, cardiopulmonary bypass-H2 group, n = 15) and a proton pump inhibitor (rabeprazole, cardiopulmonary bypass-PPI group, n = 15) in patients undergoing cardiac surgery with cardiopulmonary bypass, and also compared in patients undergoing a off-pump coronary artery bypass graft surgery (off-pump cardiopulmonary bypass-H2 group, n = 15). Gastric pH (5.14 ± 0.61) and gastric fluid volume (13.2 ± 2.4 mL) at the end of surgery in off-pump cardiopulmonary bypass-H2 groups was significantly lower and higher than those in both cardiopulmonary bypass-H2 (6.25 ± 0.54, 51.3 ± 8.0 mL) and cardiopulmonary bypass-PPI (7.29 ± 0.13, 63.5 ± 14.8 mL) groups, respectively although those variables did not differ between groups after the induction of anesthesia. Plasma gastrin (142 ± 7 pg/mL) at the end of surgery and maximal blood lactate levels (1.50 ± 0.61 mM) in off-pump cardiopulmonary bypass-H2 group were also significantly lower than those in both cardiopulmonary bypass-H2 (455 ± 96 pg/mL, 3.97 ± 0.80 mM) and cardiopulmonary bypass-PPI (525 ± 27 pg/mL, 3.15 ± 0.44 mM) groups, respectively. In addition, there was a significant correlation between gastric fluid volume and maximal blood lactate (r = 0.596). In conclusion, cardiopulmonary bypass may cause an increase in gastric fluid volume which neither H2 antagonist nor PPI suppresses. A significant correlation between gastric fluid volume and maximal blood lactate suggests that gastric fluid volume may predict degree of gastrointestinal tract hypoperfusion.
PMCID: PMC3128360  PMID: 21765601
cardiopulmonary bypass; gastrointestinal ischemia; gastric acidity; H2 antagonists; proton pump inhibitors
10.  Impact of Intermittent Apnea on Myocardial Tissue Oxygenation—A Study Using Oxygenation-Sensitive Cardiovascular Magnetic Resonance 
PLoS ONE  2013;8(1):e53282.
Carbon dioxide (CO2) is a recognized vasodilator of myocardial blood vessels that leads to changes in myocardial oxygenation through the recruitment of the coronary flow reserve. Yet, it is unknown whether changes of carbon dioxide induced by breathing maneuvers can be used to modify coronary blood flow and thus myocardial oxygenation. Oxygenation-sensitive cardiovascular magnetic resonance (CMR) using the blood oxygen level-dependent (BOLD) effect allows for non-invasive monitoring of changes of myocardial tissue oxygenation. We hypothesized that mild hypercapnia induced by long breath-holds leads to changes in myocardial oxygenation that can be detected by oxygenation-sensitive CMR.
Methods and Results
In nine anaesthetized and ventilated pigs, 60s breath-holds were induced. Left ventricular myocardial and blood pool oxygenation changes, as monitored by oxygenation-sensitive CMR using a T2*-weighted steady-state-free-precession (SSFP) sequence at 1.5T, were compared to changes of blood gas levels obtained immediately prior to and after the breath-hold. Long breath-holds resulted in an increase of paCO2, accompanied by a decrease of paO2 and pH. There was a significant decrease of blood pressure, while heart rate did not change. A decrease in the left ventricular blood pool oxygenation was observed, which was similar to drop in SaO2. Oxygenation in the myocardial tissue however, was maintained throughout the period. Changes in myocardial oxygenation were strongly correlated with the change in paCO2 during the breath-hold (r = 0.90, p = 0.010).
Despite a drop in blood oxygen levels, myocardial oxygenation is maintained throughout long breath-holds and is linearly correlated with the parallel increase of arterial CO2, a known coronary vasodilator. Breathing maneuvers in combination with oxygenation-sensitive CMR may be useful as a diagnostic test for coronary artery function.
PMCID: PMC3536756  PMID: 23301055
11.  Transaortic Intra-Aortic Balloon Pump Catheter Insertion through a Separate Saphenous Vein Graft in Patients with Severe Aortoiliac Disease 
The Scientific World Journal  2014;2014:247803.
Background. Intra-aortic balloon pump (IABP) is the most widely used mechanical assist device for hemodynamic support in high risk patients undergoing cardiac surgery. The aim of our study was to confirm whether transaortic route is a suitable alternative to allow IABP insertion in patients with severe aortoiliac diseases. Methods. This study included 7 consecutive patients undergoing coronary artery bypass grafting for severe coronary artery disease associated with severe aortoiliac disease. These patients could not be weaned from cardiopulmonary bypass and required the IABP support, which were placed through the ascending aorta. IABP catheter was inserted indirectly through a separate saphenous vein graft anastomosed to the ascending aorta by an end-to-side manner under a partial occluding clamp and advanced to the desired position in the descending thoracic aorta and exteriorly brought into the subcutaneous tissues in the jugulum. Results. The procedure was successfully performed in all the patients. The mean duration of IABP support was 54.0 ± 13.4 hours. There were no in-hospital mortality and complications related to transaortic route. IABP removal did not require repeat sternotomy. At postoperative 6th month, multislice CT examination showed thrombotic occlusion at the remnant of the saphenous vein graft. Conclusions. This technique is a simple, reliable, and reproducible option in patients with severe aortoiliac disease in whom retrograde femoral route is not possible.
PMCID: PMC3910074  PMID: 24516360
12.  Comparing the Effect of Preoperative Administration of Methylprednisolone and its Administration Before and During Surgery on the Clinical Outcome in Pediatric Open Heart Surgeries 
Cardiac surgery under Cardiopulmonary bypass causes a systemic inflammatory response with a multifactorial etiology including direct tissue damage, ischemia and stimulation of immune system induced by cardiopulmonary bypass. This study was designed due to the high prevalence and complications of this stimulated immune system in mortality, morbidity, length of ICU stay, and mechanical ventilation.
This study was aimed to compare preoperative and intraoperative methylprednisolone (MP) to intraoperative MP alone with respect to postbypass inflammation and clinical outcome.
Patients and Methods
Sixty pediatric patients (age < 5years) undergoing cardiopulmonary bypass surgery between September 2011-2012 at Imam Reza hospital-Mashhad were randomly assigned to receive preoperative and intraoperative MP (group 1: 30 mg/kg, 4 hours before bypass and in bypass prime, n = 30) or intraoperative MP only (group 2: 30 mg/kg, n = 30). Postoperative temperature (peak temperature and average temperature during the first 24 hours), amount of inotropic, duration of mechanical ventilation, ICU stay, WBC, BUN, creatinine, and CRP were recorded and compared in both groups. Data were analyzed with SPSS version 13 by T-test, Mann-Whitney test if necessary, and Chi-squared distribution.
Patient characteristics including age, weight, gender, and duration of bypass were almost similar in both groups (P > 0.05). No significant difference in amount of inotropic medications used for hemodynamic supports, duration of mechanical ventilation, peak and average temperature and length of ICU stay was observed. Among the laboratory tests (WBC, BUN, creatinine, CRP) only WBC counts raised more in group 2 when compared to group 1(P < 0.05).
There was no difference in clinical outcome after cardiac surgery when we administered an additional dose of methylprednisolone compared to a single dose of methylprednisolone.
PMCID: PMC3840835  PMID: 24349746
Cardiopulmonary Bypass; Heart Defects; Inflammation; Congenital
13.  Hypoxic and hypercapnic response in asthmatic subjects with previous respiratory failure. 
Thorax  1981;36(10):759-763.
Three children and two young adults with severe asthma who had frequent episodes of respiratory failure were studied. Isocapnic hypoxia and hyperoxic hypercapnia were produced separately using a rebreathing apparatus. Alveolar carbon dioxide tension and oxygen tension were estimated by continuously sampling expired gases. The three young children had a diminished response to hypoxia but a normal response to hypercapnia when compared to control asthmatic children (p less than 0.05) or healthy children (p less than 0.05). The two young adult patients had a normal response to hypoxia but one had a low response to hypercapnia. Studies of parents of these patients suggested that the chance combination of a possibly familial, inappropriate response to hypoxia with severe asthma would lead to a risk of respiratory failure.
PMCID: PMC471750  PMID: 7330794
14.  Feasibility of Temporary Biventricular Pacing after Off-Pump Coronary Artery Bypass Grafting in Patients with Reduced Left Ventricular Function 
Texas Heart Institute Journal  2013;40(4):403-409.
In selected patients undergoing cardiac surgery, our research group previously showed that optimized temporary biventricular pacing can increase cardiac output one hour after weaning from cardiopulmonary bypass. Whether pacing is effective after beating-heart surgery is unknown. Accordingly, in this study we examined the feasibility of temporary biventricular pacing after off-pump coronary artery bypass grafting.
The effects of optimized pacing on cardiac output were measured with an electromagnetic aortic flow probe at the conclusion of surgery in 5 patients with a preoperative mean left ventricular ejection fraction of 0.26 (range, 0.15–0.35). Atrioventricular (7) and interventricular (9) delay settings were optimized in randomized order.
Cardiac output with optimized biventricular pacing was 4.2 ± 0.7 L/min; in sinus rhythm, it was 3.8 ± 0.5 L/min. Atrial pacing at a matched heart rate resulted in cardiac output intermediate to that of sinus rhythm and biventricular pacing (4 ± 0.6 L/min). Optimization of atrioventricular and interventricular delay, in comparison with nominal settings, trended toward increased flow.
This study shows that temporary biventricular pacing is feasible in patients with preoperative left ventricular dysfunction who are undergoing off-pump coronary artery bypass grafting. Further study of the possible clinical benefits of this intervention is warranted.
PMCID: PMC3783126  PMID: 24082369
Arrhythmias, cardiac/therapy; cardiac pacing, artificial/methods; cardiac output, low/therapy; heart failure/therapy; stroke volume; ventricular dysfunction, left/complications/prevention & control
15.  Contractility of papillary muscle from rats exposed to 28 days of hypoxia, hypercapnia, and hypoxia with hypercapnia. 
Thorax  1989;44(10):808-811.
The effects of chronic respiratory failure (hypoxia and hypercapnia) on the contractile properties of cardiac muscle are not established. A study was performed of the isometric contractile properties of isolated papillary muscle removed from rats exposed in a normobaric environmental chamber to 28 days of hypoxia (fractional inspired oxygen (FIO2) 10%, fractional inspired carbon dioxide (FICO2) less than 1%), hypercapnia (FIO2 21%, FICO2 5%), and hypoxia with hypercapnia (FIO2 10%, FICO2 5%). Rats exposed to both hypoxia and hypoxia with hypercapnia developed selective right ventricular hypertrophy. Exposure to hypercapnia alone did not alter right ventricular weight. No change in right ventricular papillary muscle contractility per unit muscle mass was observed as measured by maximum active tension, maximum rate of rise or fall of tension, or time to peak tension. Rat cardiac muscle adapts successfully to the altered acid-base environment and increased work load associated with prolonged exposure to hypoxia and mild hypercapnia.
PMCID: PMC1020847  PMID: 2595623
16.  Duration of red blood cell storage and outcomes in pediatric cardiac surgery: an association found for pump prime blood 
Critical Care  2009;13(6):R207.
Cardiac surgery using cardiopulmonary bypass in newborns, infants and small children often requires intraoperative red blood cell transfusions to prime the circuit and oxygenator and to replace blood lost during surgery. The purpose of this study was to investigate the influence of red blood cell storage time prior to transfusion on postoperative morbidity in pediatric cardiac operations.
One hundred ninety-two consecutive children aged five years or less who underwent cardiac operations using cardiopulmonary bypass and who received red blood cells for priming the cardiopulmonary bypass circuit comprised the blood-prime group. Forty-seven patients receiving red blood cell transfusions after cardiopulmonary bypass were separately analyzed. Patients in the blood-prime group were divided into two groups based on the duration of storage of the red blood cells they received. The newer blood group included patients who received only red blood cells stored for less than or equal to four days and the older blood group included patients who received red blood cells stored for more than four days.
Patients in the newer blood group had a significantly lower rate of pulmonary complications (3.5% versus 14.4%; P = 0.011) as well as a lower rate of acute renal failure (0.8% versus 5.2%; P = 0.154) than patients in the older blood group. Major complications (calculated as a composite score based on pulmonary, neurological, and gastroenterological complications, sepsis and acute renal failure) were found in 6.9% of the patients receiving newer blood and 17.1% of the patients receiving older blood (P = 0.027). After adjusting for other possible confounding variables, red blood cell storage time remained an independent predictor of major morbidity. The same association was not found for patients receiving red blood cell transfusions after cardiopulmonary bypass.
The storage time of the red blood cells used for priming the cardiopulmonary bypass circuit in cardiac operations on newborns and young infants is an independent risk factor for major postoperative morbidity. Pulmonary complications, acute renal failure, and infections are the main complications associated with increased red blood cell storage time.
PMCID: PMC2811896  PMID: 20025760
17.  Cardiac Transplantation in a Jehovah's Witness 
Texas Heart Institute Journal  1988;15(3):189-191.
Between July 1982 and October 1987, surgeons at our institution performed 215 cardiac transplantation procedures, 1 of which was in a 46-year-old Jehovah's Witness with congestive cardiomyopathy, who required preoperative intra-aortic balloon pump support. At surgery, the cardiopulmonary bypass system was primed with 1600 ml of Ringer's lactate solution and dextrose. In the 57 minutes during which the patient was on cardiopulmonary bypass, the intra-aortic balloon was removed and successful orthotopic heart transplantation was performed. No supplemental blood or blood product was used, either during or after the procedure. The estimated intraoperative blood loss was 300 ml, and the postoperative chest tube drainage amounted to 1495 ml. Postoperative hematologic abnormalities (mild hypoprothrombinemia, mild thrombocytopenia, mild platelet dysfunction, and moderate hypochromic microcytic anemia) were corrected with Imferon, vitamin K, and desmopressin acetate administered intravenously, and with ferrous sulfate administered orally. This case, which to our knowledge is only the 2nd cardiac transplant in a Jehovah's Witness, further establishes that these patients can undergo even the most major of open-heart procedures without supplemental blood. (Texas Heart Institute Journal 1988;15:189-191)
PMCID: PMC324824  PMID: 15227251
Heart surgery; heart transplantation, orthotopic; cardiomyopathy, congestive; blood transfusion
18.  Comparison of Cardiac Output Responses to 2,4-Dinitrophenol-Induced Hypermetabolism and Muscular Work 
Journal of Clinical Investigation  1973;52(9):2283-2292.
Both electrically induced exercise and infusion of 2,4-dinitrophenol (DNP) increased oxygen consumption and tissue metabolism in chloralose-anesthetized dogs. Cardiac output increased with oxygen consumption at the same rate in both experimental conditions. The increase in cardiac output induced by exercise was, as expected, accompanied by increases in both lactate-to-pyruvate ratio and “excess lactate” in arterial blood. However, these parameters did not increase after DNP infusion until the rate of oxygen consumption had increased four- to fivefold, perhaps due to facilitation of mitochondrial electron transport by DNP. Anaerobic tissue metabolism therefore probably did not contribute significantly to increased cardiac output during the mild-to-moderate tissue hypermetabolism induced by DNP. The increased cardiac output may have been the result of metabolic changes common to both exercise and DNP infusion; muscular activity alone may not have been the primary determinant of the cardiac output response during exercise.
PMCID: PMC333032  PMID: 4727459
19.  Central venous oxygen saturation and blood lactate levels during cardiopulmonary bypass are associated with outcome after pediatric cardiac surgery 
Critical Care  2010;14(4):R149.
Central venous oxygen saturation and blood lactate are different indices of the adequacy of oxygen delivery to the oxygen needs. In pediatric cardiac surgery, lactate level and kinetics during and after cardiopulmonary bypass are associated with outcome variables. The aim of this study was to explore the hypothesis that the lowest central venous oxygen saturation and the peak lactate value during cardiopulmonary bypass, used alone or in combination, may be predictive of major morbidity and mortality in pediatric cardiac surgery.
We conducted a retrospective analysis of 256 pediatric (younger than 6 years) patients who had undergone cardiac surgery with continuous monitoring of central venous oxygen saturation and serial measurement of blood lactate.
Peak lactate was significantly increased when the nadir central venous oxygen saturation was < 68%. Both nadir central venous oxygen saturation and peak lactate during cardiopulmonary bypass were independently associated with major morbidity and mortality, with the same accuracy for major morbidity and a higher accuracy of peak lactate for mortality. A combined index (central venous oxygen saturation < 68% and peak lactate > 3 mmol/L) provided the highest sensitivity and specificity for major morbidity, with a positive predictive value of 89%.
The combination of a continuous monitoring of central venous oxygen saturation and serial measurements of blood lactate during cardiopulmonary bypass may offer a predictive index for major morbidity after cardiac operations in pediatric patients. This study generates the hypothesis that strategies aimed to preserve oxygen delivery during cardiopulmonary bypass may reduce the occurrence of low values of central venous oxygen saturation and elevated lactate levels. Further studies should consider this hypothesis and take into account other time-related factors, such as time of exposure to low values of central venous oxygen saturation and kinetics of lactate formation.
PMCID: PMC2945132  PMID: 20684758
20.  Relation of QRS Shortening to Cardiac Output During Temporary Resynchronization Therapy after Cardiac Surgery 
Cardiac resynchronization therapy (CRT) can improve cardiac function in heart failure without increasing myocardial oxygen consumption. However, CRT optimization based on hemodynamics or echocardiography is difficult. QRS duration (QRSd) is a possible alternative optimization parameter. Accordingly, we assessed QRSd optimization of CRT during cardiac surgery. We hypothesized that QRSd shortening during changes in interventricular pacing delay (VVD) would increase cardiac output (CO). Seven patients undergoing coronary artery bypass, aortic or mitral valve surgery with LV ejection fraction ≤ 40% and QRSd ≥ 100 msec were studied. CRT was implemented at epicardial pacing sites in the left and right ventricle and right atrium during VVD variation after cardiopulmonary bypass. QRSd was correlated with CO from an electromagnetic aortic flow probe. Both positive and negative correlations were observed. Correlation coefficients ranged from 0.70 to −0.74 during VVD testing. Clear minima in QRSd were observed in four patients and were within 40 msec of maximum CO in two. We conclude that QRSd is not useful for routine optimization of VVD after cardiac surgery but may be useful in selected patients. Decreasing QRSd is associated with decreasing CO in some patients, suggesting that CRT can affect determinants of QRSd and ventricular function independently.
PMCID: PMC3086767  PMID: 20592584
biventricular pacing; heart failure; cardiac surgery; LV power failure; low output state
21.  Haemofiltration in newborns treated with extracorporeal membrane oxygenation: a case-comparison study 
Critical Care  2009;13(2):R48.
Extracorporeal membrane oxygenation is a supportive cardiopulmonary bypass technique for patients with acute reversible cardiovascular or respiratory failure. Favourable effects of haemofiltration during cardiopulmonary bypass instigated the use of this technique in infants on extracorporeal membrane oxygenation. The current study aimed at comparing clinical outcomes of newborns on extracorporeal membrane oxygenation with and without continuous haemofiltration.
Demographic data of newborns treated with haemofiltration during extracorporeal membrane oxygenation were compared with those of patients treated without haemofiltration in a retrospective 1:3 case-comparison study. Primary outcome parameters were time on extracorporeal membrane oxygenation, time until extubation after decannulation, mortality and potential cost reduction. Secondary outcome parameters were total and mean fluid balance, urine output in mL/kg/day, dose of vasopressors, blood products and fluid bolus infusions, serum creatinin, urea and albumin levels.
Fifteen patients with haemofiltration (HF group) were compared with 46 patients without haemofiltration (control group). Time on extracorporeal membrane oxygenation was significantly shorter in the HF group: 98 hours (interquartile range (IQR) = 48 to 187 hours) versus 126 hours (IQR = 24 to 403 hours) in the control group (P = 0.02). Time from decannulation until extubation was shorter as well: 2.5 days (IQR = 0 to 6.4 days) versus 4.8 days (IQR = 0 to 121.5 days; P = 0.04). The calculated cost reduction was €5000 per extracorporeal membrane oxygenation run. There were no significant differences in mortality. Patients in the HF group needed fewer blood transfusions: 0.9 mL/kg/day (IQR = 0.2 to 2.7 mL/kg/day) versus 1.8 mL/kg/day (IQR = 0.8 to 2.9 mL/kg/day) in the control group (P< 0.001). Consequently the number of blood units used was significantly lower in the HF group (P< 0.001). There was no significant difference in inotropic support or other fluid resuscitation.
Adding continuous haemofiltration to the extracorporeal membrane oxygenation circuit in newborns improves outcome by significantly reducing time on extracorporeal membrane oxygenation and on mechanical ventilation, because of better fluid management and a possible reduction of capillary leakage syndrome. Fewer blood transfusions are needed. All in all, overall costs per extracorporeal membrane oxygenation run will be lower.
PMCID: PMC2689492  PMID: 19344497
22.  Comparison of almitrine bismesylate and medroxyprogesterone acetate on oxygenation during wakefulness and sleep in patients with chronic obstructive lung disease. 
Thorax  1990;45(9):666-669.
The effects of almitrine bismesylate and medroxyprogesterone acetate on oxygenation during wakefulness and sleep were compared in six patients with chronic obstructive lung disease and carbon dioxide retention. Patients received 1.5 mg/kg almitrine (a peripheral chemoreceptor stimulant), 100 mg of medroxyprogesterone (a central respiratory stimulant), or matched placebo daily for 15 days in random order in a crossover trial. When subjects were awake almitrine increased the ventilatory response to hypoxia and increased arterial oxygen tension (PaO2) to a greater extent than medroxyprogesterone, whereas medroxyprogesterone augmented the ventilatory response to hypercapnia and decreased arterial carbon dioxide tension (PaCO2) to a greater extent than almitrine. Neither drug influenced sleep architecture significantly, except that medroxyprogesterone increased the number of arousals. Almitrine had a more favourable effect than placebo on oxygenation as estimated from arterial oxygen saturation (SaO2) during the different stages of sleep, the number of episodes of hypoxaemia, and the amount of time that SaO2 was below 80%. The only change with medroxyprogesterone by comparison with placebo was a decrease in the number of hypoxaemic episodes. It is concluded that both active drugs improved blood gases during wakefulness, but that 1.5 mg/kg of almitrine is superior to 100 mg of medroxyprogesterone in improving SaO2 during sleep.
PMCID: PMC462687  PMID: 2145654
23.  Off-pump coronary artery bypass surgery compared with stent implantation and on-pump bypass surgery: clinical outcome and cost-effectiveness at one year 
Netherlands Heart Journal  2005;13(7-8):259-268.
Coronary revascularisation by means of surgery or percutaneous intervention plays an important role in the management of patients with ischaemic heart disease. Coronary bypass surgery without cardiopulmonary bypass (off-pump surgery) has been reintroduced into clinical practice to avoid complications related to the use of cardiopulmonary bypass. It is unknown whether off-pump surgery can match the outcomes of bypass surgery with cardiopulmonary bypass (on-pump surgery) or intracoronary stent implantation.
The Octopus study comprised two multicentre randomised trials. In the Octopump trial, on-pump surgery was compared with off-pump surgery (139 vs. 142 patients). In the Octostent trial stent implantation was compared with off-pump surgery (138 vs. 142 patients). The primary cardiac endpoint was survival free from the following cardiovascular events: stroke, myocardial infarction and repeated coronary revascularisation. Secondary endpoints included quality of life and cost-effectiveness. The uncertainty surrounding the cost-effectiveness analysis was addressed by bootstrapping.
Octopump trial: at one year, event-free survival in the on-pump group was 90.6% and in the off-pump group 88.0% (difference 2.6%, 95% CI-4.6 to 9.8). Quality-adjusted years of life were 0.83 and 0.82 (p=0.81), respectively. On-pump surgery was associated with €2089 (14.1%) additional direct medical costs per patient (p<0.01). Off-pump was more cost-effective than on-pump surgery in 95% of bootstrap estimates.
Octostent trial: at one year, event-free survival in the stent group was 85.5% and in the off-pump surgery group 91.5% (difference -6.0%, 95% CI -13.5 to 1.4). Quality-adjusted years of life were 0.82 and 0.79 (p=0.09), respectively. Stent implantation reduced direct medical costs by €2813 (26.0%) per patient (p=0.01). Stent implantation was more cost-effective in 95% of bootstrap estimates.
In selected patients eligible for bypass surgery, there was no difference in cardiac outcome between on-pump and off-pump surgery. Off-pump surgery, however, was more cost-effective than on-pump surgery and may be preferred from an economic perspective. In selected patients eligible for percutaneous coronary intervention, stent implantation was more cost-effective than off-pump surgery while maintaining comparable cardiac outcome. Therefore, stent implantation rather than off-pump surgery can be recommended as a first-choice revascularisation strategy.
PMCID: PMC2497251
bypass surgery; cost-effectiveness; off-pump; stents
24.  Postoperative cardiac arrest in children with congenital heart abnormalities 
ARYA Atherosclerosis  2013;9(2):145-149.
The exact survival rates and markers of survival after postoperative cardiac arrest in children with congenital heart abnormalities are unknown.
In this one-year study, we identified children younger than seven years of age with postoperative cardiac arrest in our pediatric cardiac intensive care unit database. Parameters from perioperative, pre-arrest, and resuscitation periods were analyzed for these patients. Comparisons were made between survivors and non-survivors after cardiopulmonary resuscitation (CPR). Fisher's exact, Student's t, and chi-square tests were used to analyze data.
Of 529 evaluated children who underwent corrective heart surgery, 59 (11%) sustained a documented cardiac arrest. Of these, 22 (37%) survived and regained their vital signs. Perioperative parameters (age, weight, and duration of cardiopulmonary bypass pumping), ventricular physiology, oxygen saturation, and bicarbonate concentration did not influence the outcome of CPR. Greater use of inotropic agents was not associated with higher mortality. A significant relationship was seen between having history of cardiac arrest and CPR success (P < 0.001).
CPR had undesirable outcomes in patients with hemodynamic dysfunction (i.e. low mean arterial blood pressure). Patients with univentricular physiology or history of cardiac arrest are not prone to a higher risk of mortality following arrest.
PMCID: PMC3653246  PMID: 23690815
Cardiac arrest; Congenital; Cardiopulmonary resuscitation; Pediatrics; Operation
25.  CARDIAC OUTPUT DURING CARDIOPULMONARY BYPASS—Animal Experiments as a Guide to Flow Rate 
California Medicine  1963;98(3):129-133.
Superior total body perfusion during cardiopulmonary bypass in dogs is achieved by duplicating, in each individual case, the actual operative cardiac output, rather than by relying on the currently recommended perfusion flow rates.
A highly accurate method of measuring the cardiac output is presented using the gated sinewave electromagnetic flowmeter. Simplicity and sensitivity of the method enable the operator to measure the flow in situ (in the intact canine ascending aorta) and thus to determine a truly representative cardiac output before the cardiopulmonary bypass is effected.
An adjustable hydraulic pump in conjunction with the electromagnetic flowmeter is used to substitute the natural cardiac action in order to maintain the normal hemodynamic state by providing a pulsatile flow of proper magnitude. The procedure is technically simple and, supported by favorable experimental evidence, is recommended for clinical use in open heart operations.
PMCID: PMC1575696  PMID: 13931159

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