Peri-operative neurological complications.

Brain injury from cardiac surgery is an important source of patient morbidity and mortality. The relationship between risk of brain injury and advanced age portends a rising frequency of these complications due to an increasing proportion of elderly patients undergoing cardiac surgery. This review will explore the aetiology and risk factors for peri-operative stroke, postoperative cognitive dysfunction and postoperative delirium. The prevention of each of these conditions will also be discussed, with a focus on brain protection strategies and the avoidance of cerebral embolism and hypoperfusion.

Association of intraoperative changes in brain-derived neurotrophic factor and postoperative delirium in older adults.

BACKGROUND: Delirium is common after surgery, although the aetiology is poorly defined. Brain-derived neurotrophic factor (BDNF) is a neurotrophin important in neurotransmission and neuroplasticity. Decreased levels of BDNF have been associated with poor cognitive outcomes, but few studies have characterized the role of BDNF perioperatively. We hypothesized that intraoperative decreases in BDNF levels are associated with postoperative delirium. METHODS: Patients undergoing spine surgery were enrolled in a prospective cohort study. Plasma BDNF was collected at baseline and at least hourly intraoperatively. Delirium was assessed using rigorous methods, including the Confusion Assessment Method (CAM) and CAM for the intensive care unit. Associations of changes in BDNF and delirium were examined using regression models. RESULTS: Postoperative delirium developed in 32 of 77 (42%) patients. The median baseline BDNF level was 7.6 ng ml -1 [interquartile range (IQR) 3.0-11.2] and generally declined intraoperatively [median decline 61% (IQR 31-80)]. There was no difference in baseline BDNF levels by delirium status. However, the percent decline in BDNF was greater in patients who developed delirium [median 74% (IQR 51-82)] vs in those who did not develop delirium [median 50% (IQR 14-79); P =0.03]. Each 1% decline in BDNF was associated with increased odds of delirium in unadjusted {odds ratio [OR] 1.02 [95% confidence interval (CI) 1.00-1.04]; P =0.01}, multivariable-adjusted [OR 1.02 (95% CI 1.00-1.03); P =0.03], and propensity score-adjusted models [OR 1.02 (95% CI 1.00-1.04); P =0.03]. CONCLUSIONS: We observed an association between intraoperative decline in plasma BDNF and delirium. These preliminary results need to be confirmed but suggest that plasma BDNF levels may be a biomarker for postoperative delirium.

Defining oliguria during cardiopulmonary bypass and its relationship with cardiac surgery-associated acute kidney injury.

BACKGROUND: While urine flow rate ≤0.5 ml kg-1 h-1 is believed to define oliguria during cardiopulmonary bypass (CPB), it is unclear whether this definition identifies risk for acute kidney injury (AKI) . The purpose of this retrospective study was to evaluate if urine flow rate during CPB is associated with AKI. METHODS: Urine flow rate was calculated in 503 patients during CPB. AKI in the first 48 h after surgery was defined by the Kidney Disease: Improving Global Outcomes classification. Adjusted risk factors associated with AKI and urine flow rate were assessed. RESULTS: Patients with AKI [n=149 (29.5%)] had lower urine flow rate than those without AKI (P<0.001). The relationship between urine flow and AKI risk was non-linear, with an inflection point at 1.5 ml kg-1 h-1 Among patients with urine flow <1.5 ml kg-1 h-1, every 0.5 ml kg-1 h-1 higher urine flow reduced the adjusted risk of AKI by 26% (95% CI 13-37; P<0.001). Urine flow rate during CPB was independently associated with the risk for AKI. Age up to 80 years and preoperative diuretic use were inversely associated with urine flow rate; mean arterial pressure on CPB (when <87 mmHg) and CPB flow were positively associated with urine flow rate. CONCLUSIONS: Urine flow rate during CPB <1.5 ml kg-1 h-1 identifies patients at risk for cardiac surgery-associated AKI. Careful monitoring of urine flow rate and optimizing mean arterial pressure and CPB flow might be a means to ensure renal perfusion during CPB. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00769691 and NCT00981474.

Evidence of an association between brain cellular injury and cognitive decline after non-cardiac surgery.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is common after non-cardiac surgery, but the mechanism is unclear. We hypothesized that decrements in cognition 1 month after non-cardiac surgery would be associated with evidence of brain injury detected by elevation of plasma concentrations of S100ß, neuron-specific enolase (NSE), and/or the brain-specific protein glial fibrillary acid protein (GFAP). METHODS: One hundred and forty-nine patients undergoing shoulder surgery underwent neuropsychological testing before and then 1 month after surgery. Plasma was collected before and after anaesthesia. We determined the relationship between plasma biomarker concentrations and individual neuropsychological test results and a composite cognitive functioning score (mean Z-score). RESULTS: POCD (≥-1.5 sd decrement in Z-score from baseline) was present in 10.1% of patients 1 month after surgery. There was a negative relationship between higher plasma GFAP concentrations and lower postoperative composite Z-scores {estimated slope=-0.14 [95% confidence interval (CI) -0.24 to -0.04], P=0.005} and change from baseline in postoperative scores on the Rey Complex Figure Test copy trial (P=0.021), delayed recall trial (P=0.010), and the Symbol Digit Modalities Test (P=0.004) after adjustment for age, sex, history of hypertension and diabetes. A similar relationship was not observed with S100ß or NSE concentrations. CONCLUSIONS: Decline in cognition 1 month after shoulder surgery is associated with brain cellular injury as demonstrated by elevated plasma GFAP concentrations.

Apparent diffusion coefficient scalars correlate with near-infrared spectroscopy markers of cerebrovascular autoregulation in neonates cooled for perinatal hypoxic-ischemic injury.

BACKGROUND AND PURPOSE: Neurologic morbidity remains high in neonates with perinatal hypoxic-ischemic injury despite therapeutic hypothermia. DTI provides qualitative and quantitative information about the microstructure of the brain, and a near-infrared spectroscopy index can assess cerebrovascular autoregulation. We hypothesized that lower ADC values would correlate with worse autoregulatory function. MATERIALS AND METHODS: Thirty-one neonates with hypoxic-ischemic injury were enrolled. ADC scalars were measured in 27 neonates (age range, 4-15 days) in the anterior and posterior centrum semiovale, basal ganglia, thalamus, posterior limb of the internal capsule, pons, and middle cerebellar peduncle on MRI obtained after completion of therapeutic hypothermia. The blood pressure range of each neonate with the most robust autoregulation was identified by using a near-infrared spectroscopy index. Autoregulatory function was measured by blood pressure deviation below the range with optimal autoregulation. RESULTS: In neonates who had MRI on day of life ≥10, lower ADC scalars in the posterior centrum semiovale (r = -0.87, P = .003, n = 9) and the posterior limb of the internal capsule (r = -0.68, P = .04, n = 9) correlated with blood pressure deviation below the range with optimal autoregulation during hypothermia. Lower ADC scalars in the basal ganglia correlated with worse autoregulation during rewarming (r = -0.71, P = .05, n = 8). CONCLUSIONS: Blood pressure deviation from the optimal autoregulatory range may be an early biomarker of injury in the posterior centrum semiovale, posterior limb of the internal capsule, and basal ganglia. Optimizing blood pressure to support autoregulation may decrease the risk of brain injury in cooled neonates with hypoxic-ischemic injury.

Arterial pressure above the upper cerebral autoregulation limit during cardiopulmonary bypass is associated with postoperative delirium.

BACKGROUND: Mean arterial pressure (MAP) below the lower limit of cerebral autoregulation during cardiopulmonary bypass (CPB) is associated with complications after cardiac surgery. However, simply raising empiric MAP targets during CPB might result in MAP above the upper limit of autoregulation (ULA), causing cerebral hyperperfusion in some patients and predisposing them to cerebral dysfunction after surgery. We hypothesized that MAP above an ULA during CPB is associated with postoperative delirium. METHODS: Autoregulation during CPB was monitored continuously in 491 patients with the cerebral oximetry index (COx) in this prospective observational study. COx represents Pearson's correlation coefficient between low-frequency changes in regional cerebral oxygen saturation (measured with near-infrared spectroscopy) and MAP. Delirium was defined throughout the postoperative hospitalization based on clinical detection with prospectively defined methods. RESULTS: Delirium was observed in 45 (9.2%) patients. Mechanical ventilation for >48 h [odds ratio (OR), 3.94; 95% confidence interval (CI), 1.72-9.03], preoperative antidepressant use (OR, 3.0; 95% CI, 1.29-6.96), prior stroke (OR, 2.79; 95% CI, 1.12-6.96), congestive heart failure (OR, 2.68; 95% CI, 1.28-5.62), the product of the magnitude and duration of MAP above an ULA (mm Hg h; OR, 1.09; 95% CI, 1.03-1.15), and age (per year of age; OR, 1.01; 95% CI, 1.01-1.07) were independently associated with postoperative delirium. CONCLUSIONS: Excursions of MAP above the upper limit of cerebral autoregulation during CPB are associated with risk for delirium. Optimizing MAP during CPB to remain within the cerebral autoregulation range might reduce risk of delirium. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT00769691 and NCT00981474.

Risks for impaired cerebral autoregulation during cardiopulmonary bypass and postoperative stroke.

BACKGROUND: Impaired cerebral autoregulation may predispose patients to cerebral hypoperfusion during cardiopulmonary bypass (CPB). The purpose of this study was to identify risk factors for impaired autoregulation during coronary artery bypass graft, valve surgery with CPB, or both and to evaluate whether near-infrared spectroscopy (NIRS) autoregulation monitoring could be used to identify this condition. METHODS: Two hundred and thirty-four patients were monitored with transcranial Doppler and NIRS. A continuous, moving Pearson's correlation coefficient was calculated between mean arterial pressure (MAP) and cerebral blood flow (CBF) velocity, and between MAP and NIRS data, to generate the mean velocity index (Mx) and cerebral oximetry index (COx), respectively. Functional autoregulation is indicated by an Mx and COx that approach zero (no correlation between CBF and MAP); impaired autoregulation is indicated by an Mx and COx approaching 1. Impaired autoregulation was defined as an Mx ≥0.40 at all MAPs during CPB. RESULTS: Twenty per cent of patients demonstrated impaired autoregulation during CPB. Based on multivariate logistic regression analysis, time-averaged COx during CPB, male gender, Pa(CO(2)), CBF velocity, and preoperative aspirin use were independently associated with impaired CBF autoregulation. Perioperative stroke occurred in six of 47 (12.8%) patients with impaired autoregulation compared with five of 187 (2.7%) patients with preserved autoregulation (P=0.011). CONCLUSIONS: Impaired CBF autoregulation occurs in 20% of patients during CPB. Patients with impaired autoregulation are more likely than those with functional autoregulation to have perioperative stroke. Non-invasive monitoring autoregulation may provide an accurate means to predict impaired autoregulation. Clinical trials registration. www.clinicaltrials.gov (NCT00769691).

Elastic vibrations in seamless microtubules.

Parameters characterizing elastic properties of microtubules, measured in several recent experiments, reflect an anisotropic character. We describe the microscopic dynamical properties of microtubules using a discrete model based on an appropriate lattice of dimers. Adopting a harmonic approximation for the dimer-dimer interactions and estimating the lattice elastic constants, we make predictions regarding vibration dispersion relations and vibration propagation velocities. Vibration frequencies and velocities are expressed as functions of the elastic constants and of the geometrical characteristics of the microtubules. We show that vibrations which propagate along the protofilament do so significantly faster than those along the helix.

Systematic genetic analysis with ordered arrays of yeast deletion mutants.

In Saccharomyces cerevisiae, more than 80% of the approximately 6200 predicted genes are nonessential, implying that the genome is buffered from the phenotypic consequences of genetic perturbation. To evaluate function, we developed a method for systematic construction of double mutants, termed synthetic genetic array (SGA) analysis, in which a query mutation is crossed to an array of approximately 4700 deletion mutants. Inviable double-mutant meiotic progeny identify functional relationships between genes. SGA analysis of genes with roles in cytoskeletal organization (BNI1, ARP2, ARC40, BIM1), DNA synthesis and repair (SGS1, RAD27), or uncharacterized functions (BBC1, NBP2) generated a network of 291 interactions among 204 genes. Systematic application of this approach should produce a global map of gene function.

Mechanisms and attenuation of hemostatic activation during extracorporeal circulation.

Patients undergoing cardiac surgery with cardiopulmonary bypass are at risk for excessive microvascular bleeding, which often leads to transfusion of allogeneic blood and blood components as well as reexploration in a smaller subset of patients. Excessive bleeding after cardiac surgery is generally related to a combination of several alterations in the hemostatic system pertaining to hemodilution, excessive activation of the hemostatic system, and potentially the use of newer, longer-acting antiplatelet or antithrombotic agents. Although several nonpharmacologic strategies have been proposed, this review summarizes the role of pharmacologic interventions as means to attenuate the alterations in the hemostatic system during CPB in an attempt to reduce excessive bleeding, transfusion, and reexploration. Specifically, agents that inhibit platelets, fibrinolysis, factor Xa and thrombin, as well as broad-spectrum agents, have been investigated with respect to their role in reducing consumption of clotting factors and better preservation of platelet function. Prophylactic administration of agents with antifibrinolytic, anticoagulant, and possibly antiinflammatory properties can decrease blood loss and transfusion. Although aprotinin seems to be the most effective blood conservation agent (which is most likely related to its broad-spectrum nature), agents with isolated antifibrinolytic properties may be as effective in low-risk patients. The ability to reduce blood product transfusions and to decrease operative times and reexploration rates favorably affects patient outcomes, availability of blood products, and overall health care costs.

Cardiac and neurologic complications identify risks for mortality for both men and women undergoing coronary artery bypass graft surgery.

BACKGROUND: Despite a number of studies showing that women and men respond to coronary artery bypass graft surgery differently, it is not known whether variables associated with mortality are the same for women and men. The purpose of this study was to identify variables independently associated with mortality for women undergoing coronary artery bypass graft surgery. METHODS: Single-institutional data were prospectively collected from 5,113 patients (1,558 or 30.5% women) undergoing coronary artery bypass graft surgery. The database was reviewed for patient characteristics and operative outcomes based on sex. Complications evaluated included low cardiac output syndrome (cardiac index < 2.0 l x min(-1) x m(-2) for > 8 h, regardless of treatment), stroke (new permanent global or focal motor deficits), Q-wave myocardial infarction, postoperative atrial fibrillation, and operative mortality. RESULTS: Women were older than men, and they were more likely to have preexisting hypertension, diabetes, and a history of stroke. Operative mortality for women was higher than for men (3.5% vs. 2.5%, P < 0.05). Compared with men, women were more likely to experience a postoperative myocardial infarction, stroke, and low cardiac output syndrome. When performing analysis on data from both sexes separately, low cardiac output syndrome, new stroke, myocardial infarction, and duration of cardiopulmonary bypass were independently associated with mortality for women and men both. Patient age was not independently associated with risk for mortality for women, but it was for men. However, when the authors combined both sexes in the logistic regression analysis, the age-sex interaction was not significant (P = 0.266), indicating that there was insufficient evidence to assert that age has a different effect on mortality for men and women. CONCLUSIONS: These data confirm that women have higher perioperative mortality after coronary artery bypass graft surgery compared with men. A higher frequency of cardiac and neurologic complications seem to account to a large extent for the higher operative mortality for women. Factors independently associated with perioperative mortality are generally similar for women and men.

VISTRAJ: exploring protein conformational space.

UNLABELLED: VISTRAJ is an application which allows 3D visualization, manipulation and editing of protein conformational space using probabilistic maps of this space called 'trajectory distributions'. Trajectory distributions serve as input to FOLDTRAJ which samples protein structures based on the represented conformational space. VISTRAJ also allows FOLDTRAJ to be used as a tool for homology model creation, and structures may be generated containing post-translationally modified amino acids. AVAILABILITY: Binaries are freely available for non-profit use as part of the FOLDTRAJ package at ftp://ftp.mshri.on.ca/pub/TraDES/foldtraj/.

Occurrence of myocardial ischemia immediately after coronary revascularization using radial arterial conduits.

OBJECTIVE: To assess the incidence of myocardial ischemia in patients receiving radial arterial and left internal thoracic arterial conduits (RA+LITA) during the postrevascularization period. DESIGN: Nonrandomized observational sequential cohort. SETTING: University hospital. PARTICIPANTS: Thirty adult patients, scheduled for elective coronary artery bypass graft surgery with RA+LITA, compared with 30 patients who received saphenous vein graft and left internal thoracic arterial conduits. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Myocardial ischemic episodes were defined as reversible ST-segment depressions or elevations >or=1 mm and >or=2 mm at J +60 msec and lasting >or=1 minute using 2-channel Holter monitoring. During the post-cardiopulmonary bypass period, a significantly higher number of patients with >or=2 mm ischemic episodes (21.7%; p = 0.015) and higher number of >or=2 mm ischemic episodes per hour (0.19 +/- 0.4 episodes/hr; p = 0.03) were observed in the radial artery group versus the comparison group (0% of patients and 0 episodes/hr). During the postoperative period (24 hours), a significantly longer duration of >or=2 mm ischemic episodes was observed in the radial artery group (24 +/- 33 minutes v 8.4 +/- 21 minutes; p = 0.046). Radial artery graft, preoperative calcium antagonists, and pulmonary arterial mean pressure were independent predictors of the duration and area under the ST-segment curve of >or=2 mm ischemic episodes during the postoperative period. CONCLUSION: There is an association between the use of the radial artery graft and the incidence and severity of >or=2 mm postrevascularization ischemic episodes.

Atrial fibrillation after coronary artery bypass graft surgery is unrelated to cardiac abnormalities detected by transesophageal echocardiography.

UNLABELLED: Atrial fibrillation is a common complication of coronary artery bypass graft (CABG) surgery that is associated with adverse patient outcomes. We evaluated whether preexisting abnormalities of cardiac structure or function detected with transesophageal echocardiography (TEE) are prevalent in patients later developing atrial fibrillation after CABG surgery. TEE imaging was performed after induction of general anesthesia, but before primary CABG surgery, in 62 consecutive patients without cardiac valvular disease or preexisting atrial fibrillation. Measurements included left atrial diameter, left ventricular wall thickness, left ventricular end-systolic and end-diastolic dimensions and fractional area change. Pulsed-wave Doppler measurements of pulmonary venous and trans-mitral blood flow velocity were obtained. Continuous monitoring with telemetry electrocardiography for the development of atrial fibrillation was performed. Eighteen patients (29%) developed postoperative atrial fibrillation. There were no significant differences in left atrial or left ventricular TEE variables or pulsed-wave Doppler pulmonary venous flow measurements between patients with and without postoperative atrial fibrillation. After adjusting for age and duration of aortic cross-clamping, there were no differences in the transmitral Doppler diastolic filling variables between these same groups. These data suggest that atrial fibrillation commonly occurs after CABG surgery in the absence of atrial enlargement or Doppler-derived cardiac functional abnormalities. The data imply that the use of TEE immediately before surgery would be an insensitive means for routine identification of patients susceptible to this arrhythmia. IMPLICATIONS: Transesophageal echocardiography performed immediately before coronary artery bypass graft (CABG) surgery is not useful for prediction of susceptibility to develop atrial fibrillation postoperatively. Postoperative atrial fibrillation commonly occurs after CABG surgery in the absence of preoperative atrial enlargement or Doppler derived functional abnormalities.

The relationship between hirudin and activated clotting time: implications for patients with heparin-induced thrombocytopenia undergoing cardiac surgery.

UNLABELLED: Anticoagulation with recombinant hirudin (r-hirudin) (Refludan) has been suggested as an alternative to heparin for patients with heparin-induced thrombocytopenia requiring cardiac surgery. We sought to develop a modified activated coagulation time (ACT) that would allow quantification of the levels of r-hirudin required during cardiopulmonary bypass (CPB). Twenty-one patients scheduled for elective cardiac surgical procedures requiring CPB were enrolled in this IRB-approved study. R-hirudin was added to blood specimens obtained before heparin administration (before CPB) and 30 min after heparin neutralization with protamine (after CPB) to result in concentrations of 0, 2, 4, 6, 7, or 8 microg/mL. Kaolin/ACT and complete blood count measurements were assayed in native specimens (first 10 patients, Phase I) or in specimens mixed with equal volumes of commercial normal plasma (second 11 patients, Phase II). In Phase I, good (r(2) = 0.83) linear relationships between ACT values and r-hirudin concentrations (< or =4 microg/mL) were observed in specimens obtained before CPB. However, ACT values were markedly prolonged (P < 0.0001) by r-hirudin in specimens obtained after CPB, with ACT values generally exceeding the ACT's detection limit (>999 s) at hirudin concentrations >2 microg/mL. In patient specimens mixed with normal plasma (Phase II), ACT/hirudin relationships (i.e., hirudin/ACT slope values obtained with hirudin concentration < or =4 microg/mL) in the post-CPB period (0.022 +/- 0.004 microg. mL(-1). s(-1)) were similar (P = 0.47) to those (0.019 +/- 0.004 microg. mL(-1). s(-1)) obtained in the pre-CPB period. Accordingly, a significant relationship between normal plasma-supplemented ACT values and predilution hirudin concentration was obtained in the post-CPB (hirudin = 0.039ACT - 4.34, r(2) = 0.91) period. Although our data demonstrate that the ACT test cannot be used to monitor hirudin during CPB, the addition of 50% normal plasma to post-CPB hemodiluted blood specimens yields a consistent linear relationship between hirudin concentration and ACT values up to a predilution concentration of 8 microg/mL. Plasma-modified ACT may be useful in monitoring hirudin anticoagulation during CPB. IMPLICATIONS: A modified activated clotting time test system that may be helpful in monitoring hirudin anticoagulation in patients with heparin-induced thrombocytopenia during cardiac surgery with cardiopulmonary bypass is described.

Sex differences in neurological outcomes and mortality after cardiac surgery: a society of thoracic surgery national database report.

BACKGROUND: The purpose of this study was to evaluate whether women undergoing cardiac surgery are more likely to suffer neurological complications than men and whether these complications could explain, at least in part, their higher perioperative mortality. METHODS AND RESULTS: The Society of Thoracic Surgery National Cardiac Surgery Database was examined for the years 1996 and 1997 to determine the frequency of new neurological events (stroke, transient ischemic attack, or coma) occurring after cardiac surgery. We reviewed clinical information on 416 347 patients (32% women) for whom complete neurological outcome data were available. New neurological events after surgery were higher for women than for men (3.8% versus 2.4%, P=0.001). For the whole group, the 30-day mortality was higher for women than for men (5.7% versus 3.5%, P=0.001), and among those patients who suffered a perioperative neurological event, mortality was also significantly higher for women than men (32% versus 28%, P=0.001). After adjustment for other risk factors (eg, age, history of hypertension and/or diabetes, duration of cardiopulmonary bypass, and other comorbid conditions) by multivariable logistic regression, female sex was independently associated with significantly higher risk of suffering new neurological events after cardiac surgery (OR 1.21, 95% CI 1.14 to 1.28, P=0.001). CONCLUSIONS: Women undergoing cardiac surgery are more likely than men to suffer new perioperative neurological events, and they have higher 30-day mortality when these complications occur. The higher incidence of perioperative neurological complications in women cannot be explained by currently known risk factors.

Flow dependency of error in thermodilution measurement of cardiac output during acute tricuspid regurgitation.

OBJECTIVE: To evaluate the effect of variable degrees of tricuspid regurgitation on thermodilution cardiac output measurements during changes in venous return. DESIGN: Prospective, controlled animal study. SETTING: University laboratory. PARTICIPANTS: Eight anesthetized mongrel dogs instrumented for simultaneous measurement of cardiac output by thermodilution and ascending aortic electromagnetometry. INTERVENTIONS: Data were collected before and after induction of moderate and severe tricuspid regurgitation. Under each condition, measurements were obtained at baseline and after opening 2 peripheral arteriovenous shunts to increase venous return. MEASUREMENTS AND MAIN RESULTS: Baseline electromagnetic flow ranged from 1.74 to 3.62 L/min (median 2.73 L/min). Moderate and severe regurgitation reduced median electromagnetic flow values by 31% and 51%. Applying generalized estimating equations to model thermodilution cardiac output as a function of electromagnetic flow, arteriovenous shunt, and severity of tricuspid regurgitation revealed that (1) moderate and severe regurgitation changed the slope and intercept of the thermodilution/electromagnetic regression, but the differences between them were not significant, and (2) arteriovenous shunt alone had no effect under any condition. A simplified model independent of shunt and containing just 2 levels of tricuspid regurgitation (none or present) crossed with electromagnetic flow was applied. This analysis showed that regurgitation caused thermodilution to significantly underestimate electromagnetic flow at cardiac outputs > 2.27 L/min (99 mL/kg/min) and overestimate it at flows < 1.02 L/min (44 mL/kg/min). CONCLUSIONS: These data show that acute tricuspid regurgitation may produce underestimation of cardiac output by thermodilution when flow is relatively high, produce overestimation when flow is relatively low, or have minimal effect when flow is in the midrange.