Allow elective ventilation to recruit more organ donors.

Transplantation surgery started >50 years ago and has developed into an established medical practice in many countries. We consider it positive if our dead body could be used as an organ or tissue donor. If transplanted, our organs confer other human beings with a longer and better life. There is, however, a relative lack of organs compared with the needs, and many potential recipients die while on the waiting list for transplantation.

Thermogenic effect of amino acids not demonstrated in heart surgery with cardiopulmonary bypass.

BACKGROUND: In abdominal surgery and in healthy volunteers, amino acids increased thermogenesis. In this double-blind study we investigated if a similar effect would ensue in heart surgery and accelerate the rewarming process postoperatively. METHODS: Thirty-four patients undergoing coronary artery bypass grafting or aortic valve replacement were randomized into two groups, and received either 500 ml of amino acids or Ringer's solution intravenously during 4 h. The infusion was started approximately 30 min before the end of a cardiopulmonary bypass (CPB), performed at a temperature of 34 degrees C with rewarming to 36-37 degrees C. The lowest pulmonary artery (PA) temperature after the CPB and the time interval until the temperature reached 37 degrees C were recorded. Oxygen uptake was calculated from cardiac output (thermodilution) and the pulmonary av-difference of oxygen after induction of anaesthesia, at the end of surgery, and 1 and 2 h after the CPB. RESULTS: Demographic data, medication including beta-blockers, CPB data and case mix were similar. The lowest temperature after the CPB was 35.9 +/- 0.1 degrees C in the amino acid group and 35.6 +/- 0.2 degrees C in the control group, and the increase per hour was 0.6 +/- 0.1 degrees C and 0.6 +/- 0.0 degrees C, respectively, with no differences between the groups. During the infusion, oxygen uptake was higher in the amino acid group, 115 +/- 4 ml m(-2), than in the controls, 102 +/- 3 ml m(-2) (P < 0.05). No adverse effects of the infusions were noted. CONCLUSION: The lack of a thermal effect of the amino acids in the heart surgery was most probably due to the temperature gradients between the different body compartments, and also may have been due to the use of beta-blockers.

Brain death: an important paradigm shift in the 20th century.

The description of death in medical or pathophysiological terms changed during the last century. The focus of attention shifted from the condition of the heart to the state of the brain. The current paper investigates the time period from 1866, when the effects of an increased intracranial pressure (ICP) were studied experimentally, to 1967, when the first heart transplantation was performed. Between 1894 and 1965 four neurosurgeons: Horsley in England, Cushing in USA, Wertheimer in France and Frykholm in Sweden made important contributions. Documented discussions, if ventilator treatment should be stopped in patients with a dead brain and a beating heart, began in 1959. However, already during the latter part of the 19th century it was shown that the heart could continue to beat if artificial ventilation was performed, when spontaneous respiration had ceased due to a high ICP. Furthermore, brain death was by chance implemented in clinical practice in heart surgery with cardiopulmonary bypass (CPB) some years before the expressions 'death of the nervous system' and 'brain death' were coined.

High serum S100B levels for trauma patients without head injuries.

OBJECTIVE: Studies of patients with head trauma have demonstrated a correlation between a serum marker of brain tissue damage, namely S100B, and neuroradiological findings. It was recently demonstrated that the increases in serum S100B levels after heart surgery have extracerebral origins, probably surgically traumatized fat, muscle, and bone marrow. The current study examined multitrauma patients without head trauma, to determine whether soft-tissue and bone damage might confound the interpretation of elevated serum S100B concentrations for patients after head trauma. METHODS: A commercial assay was used to determine serum S100B concentrations for a normal population (n = 459) and multitrauma patients without head injury (n = 17). Concentrations of the two subtypes of S100B (S100A1B and S100BB) were determined using separate noncommercial assays. RESULTS: The mean serum S100B concentration for a normal healthy population was 0.032 microg/L (median, 0.010 microg/L; standard deviation, 0.040 microg/L). The upper 97.5% and 95% reference limits were 0.13 and 0.10 microg/L, respectively. No major age or sex differences were observed. Among trauma patients, serum S100B levels were highest after bone fractures (range, 2-10 microg/L) and thoracic contusions without fractures (range, 0.5-4 microg/L). Burns (range, 0.8-5 microg/L) and minor bruises also produced increased S100B levels. S100A1B and S100BB were detected in all samples. CONCLUSION: Trauma, even in the absence of head trauma, results in high serum concentrations of S100B. Interpretation of elevated S100B concentrations immediately after multitrauma may be difficult because of extracerebral contributions. S100B may have a negative predictive value to exclude brain tissue damage after trauma. Similarly, nonacute S100B measurements may be of greater prognostic value than acute measurements.

Increase in serum S100A1-B and S100BB during cardiac surgery arises from extracerebral sources.

BACKGROUND: Elevated levels of serum S100B after coronary artery bypass grafting may arise from extracerebral contamination. Serum S100B content was analyzed in several tissues, and the two dimers S100A1-B and S100BB were analyzed separately in blood. METHODS: Serum, shed blood, marrow, fat, and muscle were studied in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass using suction either to the cardiotomy reservoir (group 1, n = 10) or to a cell-saving device (group 2, n = 10), or operated on off-pump (group 3, n = 10). RESULTS: Serum S100B was sixfold higher in group 1 than in groups 2 and 3, which were identical. The same ratio between S100A1-B and S100BB was found in all groups. When compared with serum, S100B was 10(2) to 10(4) times higher in marrow, fat, muscle tissue, and shed blood. CONCLUSIONS: Separate analysis of S100A1-B and S100BB did not distinguish between S100B of cerebral and extracerebral origin. The concept that S100B only originates in astroglial and Schwann cells is wrong. Fat, muscle, and marrow in mediastinal blood contain high levels of S100B. Cardiopulmonary bypass caused no increase in S100B.

No effect of L-arginine supplementation on pulmonary endothelial dysfunction after cardiopulmonary bypass.

BACKGROUND: Acetylcholine is an endothelium-dependent vasodilator through the L-arginine-nitric oxide pathway. After ischemia-reperfusion this effect is attenuated, also demonstrated in the pulmonary circulation after cardiopulmonary bypass. Administration of L-arginine has been shown to have a protective effect on endothelial function in reperfusion injury. The aim of the current study was to test the possible effect of L-arginine on the acetylcholine reactivity in the pulmonary circulation after cardiopulmonary bypass. METHODS: Thirty-five patients with ischemic and/or valvular heart disease were investigated in a randomized, double-blinded, placebo-controlled study. The patients were divided into three groups. Group 1: high dose L-arginine (n=10), group 2: low dose L-arginine (n=10), group 3: placebo, no L-arginine, (n=15). The acetylcholine reactivity was tested with measurements of pulmonary vascular resistance before surgery and 1, 2 and 3-4 h after cardiopulmonary bypass. RESULTS: After cardiopulmonary bypass an attenuation of the acetylcholine reactivity over time was observed in all groups, with no differences between groups. CONCLUSION: In the current study L-arginine had no protective effect on the pulmonary endothelium after cardiopulmonary bypass, measured as reactivity to an infusion of acetylcholine.

Better preserved pulmonary endothelium-dependent vasodilation with off-pump coronary surgery.

OBJECTIVE: To investigate if endothelium-dependent vasodilation in the pulmonary circulation was better maintained after off-pump coronary artery bypass grafting (CABG). An impaired pulmonary vascular response to acetylcholine has been observed after cardiopulmonary bypass (CPB) in children, adults and experimentally. DESIGN: Fourteen patients operated off-pump were compared with 21 patients undergoing conventional CABG with CPB. The indexed pulmonary vascular resistance was measured before and during an infusion of acetylcholine, aiming at a concentration of 10(-6) mol/l in the pulmonary artery. Twelve patients operated on-pump received saline instead of acetylcholine. RESULTS: Before surgery pulmonary vascular resistance decreased during infusion of acetylcholine by 28% and 25% in the off-pump and on-pump groups. After surgery the decrease was 16% and 6%, respectively (p = 0.028 and p < 0.001, compared to preoperative response). The response did not differ between the two groups before, but did so after surgery (p = 0.01). Saline had no effect. CONCLUSION: The better maintained endothelium-dependent vasodilation in the off-pump group indicated less endothelial dysfunction.

The effect of cardiotomy suction on the brain injury marker S100beta after cardiopulmonary bypass.

BACKGROUND: An increase of S100beta in serum during cardiopulmonary bypass (CPB) has been interpreted as a sign of brain injury. Cardiotomy suction may cause fat embolization, and its role in the S100beta increase was examined. METHODS: Twenty coronary artery operation patients were randomly assigned to two groups, 10 with suction during CPB to cardiotomy reservoir (CR), 10 to cell saving device (CS). S100beta was measured (immunoassay) in blood from the patients and from cell saving device after processing. In 7 additional patients S100beta was measured in the cell saving device before processing and directly from the wound at sternotomy. RESULTS: Before anesthesia, serum S100beta was 0.03+/-0.06 microg/L. At the end of CPB it was 2.47+/-1.31 microg/L and 0.44+/-0.27 microg/L (CR vs CS; p < 0.001). S100beta was 33+/-12 microg/L in CS reservoir and 42+/-18 microg/L in blood from the wound. CONCLUSIONS: Most serum S100beta after CPB with cardiotomy suction may be of extracerebral origin. S100beta after CPB with cell saving device was the same as after off-pump operation. The interpretation that an increase in S100beta during CPB in patients reflects cerebral injury must be questioned.

Increased extracellular brain water after coronary artery bypass grafting is avoided by off-pump surgery.

OBJECTIVE: To determine if coronary artery bypass graft (CABG) surgery without cardiopulmonary bypass (CPB) avoids the brain swelling known to occur after CPB, to quantify these brain water compartment changes, and to identify the water shifts as due to intracellular or extracellular water. DESIGN: Prospective, controlled, and blinded. SETTING: Cardiac surgical unit in a university teaching hospital. SUBJECTS: Patients scheduled for CABG who were assigned to conventional (n = 10) or off-pump (n = 7) surgery according to their coronary anatomy. INTERVENTIONS: Magnetic resonance imaging (MRI) examinations were performed 1 day before surgery and 1 hour and 1 week after CABG surgery. MAIN OUTCOME MEASURES: Extracellular and intracellular water homeostasis was described quantitatively by calculating the averaged apparent diffusion coefficient of brain water using diffusion-weighted MRI. Blinded visual ordering of the images from the three examinations was performed according to brain size using conventional MRI. RESULTS: The average diffusion coefficient of brain water increased 4.7%+/-1.5% immediately after CABG with CPB and normalized after 1 week but did not change after CABG without CPB. No focal ischemic changes were seen in either group, and no gross neurologic deficits were observed. Visual analysis showed consistent brain swelling after CPB and variable changes in those operated without CPB. CONCLUSION: Changes consistent with increased extracellular brain water seen after CABG with CPB were not observed in patients undergoing CABG without CPB. The clinical significance of brain water changes and increased brain water content after surgery with CPB remains undefined.

Decreased pulmonary vascular resistance during nasal breathing: modulation by endogenous nitric oxide from the paranasal sinuses.

Nitric oxide is present in high concentration in the human nasal airways. During inspiration through the nose a bolus is transported to the lungs. In a randomized cross-over study the effect of two different patterns of breathing, nasal breathing and mouth breathing, was evaluated in 10 patients (mean age 65 years), breathing room air the morning of the first post-operative day after open heart surgery. Nasal breathing is defined as inspiration through the nose and expiration through the mouth, whilst mouth breathing is the converse of this: inspiration through the mouth and expiration through the nose. Pressure in the pulmonary artery and left atrium or pulmonary artery wedge was measured together with thermodilution cardiac output and arterial and mixed venous oxygenation and acid-base parameters. Pulmonary vascular resistance index (PVRI), venous admixture and alveolar-arterial gradient were calculated. Nasal breathing resulted in a lower PVRI, 256 dyn s cm-5 cm-2 vs. 287 (P < 0.01). The oxygen and carbon dioxide tension and pH of arterial and mixed venous blood, venous admixture and the alveolar-arterial gradient remained unchanged. The decreased level of PVRI during nasal breathing compared to that during mouth breathing supports the notion, that endogenous nitric oxide acts as an airborne messenger to modulate the pulmonary vascular tone during normal breathing.

Altered reactivity to acetylcholine in the pulmonary circulation after cardiopulmonary bypass is part of reperfusion injury.

STUDY OBJECTIVE: To investigate whether a time sequence of acetylcholine (ACH) reactivity indicative of endothelial reperfusion injury could be demonstrated in the pulmonary circulation in patients after cardiopulmonary bypass (CPB). DESIGN: Prospective study. SETTING: Operating theater and intensive care unit of a university hospital. PATIENTS: 10 ASA physical status III and IV patients with ischemic or valvular heart disease. INTERVENTIONS: Pulmonary vascular resistance index (PVRI) was measured before and during an infusion of ACH. This procedure was done after induction of anesthesia but before surgery, immediately after weaning from bypass, and at 1 to 1.5 and 4 hours after CPB. MEASUREMENTS AND MAIN RESULTS: ACH caused a decrease in PVRI before (p < 0.01) and directly after CPB (p < 0.05) but not at 1 to 1.5 or 4 hours after bypass. CONCLUSIONS: The maintained reactivity to ACH directly after CPB, followed by no reaction at 1 to 1.5 and 4 hours, was in agreement with experimental findings and indicates endothelial reperfusion injury caused by the period with no blood flow through the pulmonary artery during CPB and subsequent reperfusion.

Acetylcholine reactivity in the pulmonary artery during cardiac surgery in patients with ischemic or valvular heart disease.

OBJECTIVE: During cardiopulmonary bypass, there is almost no blood flow through the pulmonary artery. Ischemia and reperfusion are known to attenuate the reaction to acetylcholine. An attenuated reactivity to acetylcholine in the pulmonary circulation after cardiopulmonary bypass was previously shown in children. The current study in adult patients was designed to analyze the change over time of acetylcholine reactivity after cardiac surgery. DESIGN: A prospective study. SETTING: The operating room and intensive care unit of a university hospital. PARTICIPANTS: Eighteen patients with ischemic or valvular heart disease. INTERVENTIONS: Pulmonary vascular resistance was measured with a pulmonary artery catheter before and during an infusion of acetylcholine. This procedure was done after induction of anesthesia before surgery and 1, 4, 8, and 20 to 24 hours after cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Pulmonary vascular resistance index decreased during infusion of acetylcholine before surgery by 27% from 286 +/- 27 dyne/sec/cm-5/m2 (mean and standard error of mean) to 209 +/- 28 and at 8 and 20 to 24 hours by 23% and 34%, respectively, 288 +/- 27 to 221 +/- 29 and 229 +/- 22 to 150 +/- 17 (p < 0.001, paired t-test). One and 4 hours after cardiopulmonary bypass, no significant decrease was observed. CONCLUSIONS: These results confirm the finding of altered reactivity to acetylcholine in the pulmonary circulation after cardiopulmonary bypass. In view of the often prolonged tendency toward pulmonary hypertension observed in children, the recovery at 8 hours after surgery was unexpectedly rapid. The attenuated response to acetylcholine is most likely explained by relative ischemia in the pulmonary circulation during cardiopulmonary bypass.

Inhalation of nasally derived nitric oxide modulates pulmonary function in humans.

The vasodilator gas nitric oxide (NO) is produced in the paranasal sinuses and is excreted continuously into the nasal airways of humans. This NO will normally reach the lungs with inspiration, especially during nasal breathing. We wanted to investigate the possible effects of low-dose inhalation of NO from the nasal airways on pulmonary function. The effects of nasal and oral breathing on transcutaneous oxygen tension (tcPO2) were studied in healthy subjects. Furthermore, we also investigated whether restoring low-dose NO inhalation would influence pulmonary vascular resistance index (PVRI) and arterial oxygenation (PaO2) in intubated patients who are deprived of NO produced in the nasal airways. Thus, air derived from the patient's own nose was aspirated and led into the inhalation limb of the ventilator. In six out of eight healthy subjects tcPO2 was 10% higher during periods of nasal breathing when compared with periods of oral breathing. In six out of six long-term intubated patients PaO2 increased by 18% in response to the addition of nasal air samples. PVRI was reduced by 11% in four of 12 short-term intubated patients when nasal air was added to the inhaled air. The present study demonstrates that tcPO2 increases during nasal breathing compared with oral breathing in healthy subjects. Furthermore, in intubated patients, who are deprived of self-inhalation of endogenous NO. PaO2 increases and pulmonary vascular resistance may decrease by adding NO-containing air, derived from the patient's own nose, to the inspired air. The involvement of self-inhaled NO in the regulation of pulmonary function may represent a novel physiological principle, namely that of an enzymatically produced airborne messenger. Furthermore, our findings may help to explain one biological role of the human paranasal sinuses.

Hepatic blood flow and right ventricular function during cardiac surgery assessed by transesophageal echocardiography.

OBJECTIVE: To determine the effect of cardiopulmonary bypass (CPB) on hepatic blood flow (HBF) and the hepatic venous flow pattern. DESIGN: Single-arm prospective study. SETTING: University hospital operating room and intensive care unit. PARTICIPANTS: Eight patients ranging in age from 57 to 73 years undergoing cardiac surgery. INTERVENTIONS: Transesophageal echocardiography (TEE) was used to assess HBF before, during, and after CPB by pulsed-wave Doppler ultrasound recordings of hepatic venous flow velocity and two-dimensional recordings of the hepatic vein diameter. Hepatic vein oxygenation was monitored by hepatic vein catheterization, and gastric intramucosal pH (pHi) was followed by tonometry. MEASUREMENTS AND MAIN RESULTS: The HBF was unchanged after the start of CPB but was reduced from the baseline value 415 (standard error of the mean 40) mL/min to 225 (25) mL/min during hypothermic CPB (p < 0.05). Cardiac index, right ventricular ejection fraction, and arterial and tonometric pH were essentially unchanged during the study period. Hepatic vein and mixed venous saturation were unchanged compared to control during CPB and were reduced at 2 and 3 hours after CPB (p < 0.01). Six of the patients had a normal predominant systolic flow pattern before surgery. In the postoperative period, seven patients showed an abnormal predominant diastolic filling pattern. CONCLUSIONS: TEE represents a useful tool in assessing changes in the hepatic blood flow. The HBF was reduced during hypothermic CPB, but this was not accompanied by a reduced pHi. The changes in the venous flow pattern with a reduction in systolic flow could be explained by impaired atrial relaxation.

Clinical estimation of left and right ventricular volume with open chest compared with transesophageal echocardiography and fast-response thermodilution.

OBJECTIVE: A clinical measure--inspection of the relation of the heart (acute margin) to the diaphragm--has shown a strong positive correlation to transesophageal echocardiographic (TEE) determination of left ventricular end-diastolic area (LVEDA) during weaning from cardiopulmonary bypass (CPB). The present study examines the correlation between right ventricular end-diastolic volumes (RVEDV) before and after CPB when using the same clinical measure of left ventricular dimension. DESIGN: Prospective study. SETTING: Operating room, university hospital. PARTICIPANTS: Patients scheduled for elective coronary artery bypass grafting. INTERVENTIONS: After induction of anesthesia and endotracheal intubation, a transesophageal echo-probe was inserted. A pulmonary artery right ventricular ejection fraction/volumetric TD catheter was placed in the pulmonary artery. MEASUREMENTS AND MAIN RESULTS: Before going on CPB, a mark was made with cautery at the line of contact between the acute margin and the diaphragm. After CPB, the patients were transfused to the same level. At these two times, TEE recordings of the LVEDA and hemodynamic measurements including calculations of RVEDV were obtained. The LVEDA before and after CPB showed a positive correlation, r = 0.81, p < 0.001. The RVEDV after CPB showed a weak correlation, r = 0.54, p < 0.05, to RVEDV before CPB. There were no significant changes in right ventricular (RV) wall tension calculated as right atrial pressure x RVEDV and pulmonary artery systolic pressure x right ventricular end-systolic volume products. The only significant change regarding hemodynamic parameters was a decrease in mean arterial pressure. CONCLUSIONS: It is concluded that there is only a weak correlation regarding RVEDV before and after CPB when the patient is transfused to the line of contact, whereas this clinical measure correlates well with LVEDA.