Perioperative goal-directed haemodynamic therapy based on flow parameters: a concept in evolution.

Haemodynamic management incorporating direct or surrogate stroke volume monitoring has experienced a rapid evolution, because of emergence of the "goal-directed therapy" concept and technological developments aimed at providing a parameter leading to the goal. Nonetheless, consensus on both definitions of the ideal "goal" and strategies for achieving it remain elusive. For this review, we first consider basic physiological and patient monitoring factors relevant to the concept of "fluid responsiveness", and then focus upon randomized controlled trials and meta-analyses involving goal-directed haemodynamic therapy based on various flow parameters. Finally, we discuss the current status of noninvasive methods for monitoring fluid responsiveness.

Non-invasive cardiac output monitoring for cesarean delivery under epidural anesthesia in a patient with Marfan syndrome and cardiomyopathy.

Maternal cardiac output and stroke volume increase significantly at the time of cesarean delivery. Parturients with baseline myocardial dysfunction are at increased risk of cardiovascular decompensation in the peripartum period and close hemodynamic monitoring is warranted. We report our use of intraoperative non-invasive cardiac output monitoring during cesarean delivery under epidural anesthesia in a 24-year-old woman with dilated cardiomyopathy secondary to Marfan syndrome, aortic arch, aortic valve and mitral valve replacements and a left ventricular ejection fraction of 37%. Three distinct hemodynamic trends were noted. After achieving adequate surgical anesthesia with 2% lidocaine 20mL, cardiac output and stroke volume rose for approximately 20min from baseline values of 6.3L/min and 69mL, respectively, to 9L/min and 107mL. Values subsequently trended down and remained depressed for nearly 20min following delivery. The lack of immediate post-delivery increases in both cardiac output and stroke volume were attributed to acute blood loss, intravascular volume depletion from fluid restriction, and slow infusion of oxytocin. By the end of surgery, cardiac output and stroke volume ultimately increased by 66% and 84% of baseline values, respectively. Systemic blood pressure, heart rate and cardiac output did not appear to correlate despite the use of phenylephrine to manage hypotension. The patient remained hemodynamically stable with no evidence of acute volume overload.

Minimally invasive surgical techniques in the treatment of lung cancer.

Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related mortality worldwide. Despite recent advances in molecular characterization, targeted and adjuvant therapies of NSCLC, surgical resection remains the mainstay of curative treatment. Minimally invasive video-assisted thoracic surgery (VATS) techniques, in particular VATS lobectomy, are being increasingly utilized over traditional thoracotomy approaches in the treatment of localized NSCLC for the reported benefits with respect to postoperative recovery and the conviction of oncologic equivalence. This article will review the major VATS procedures, including their development, outcomes, and purported advantages over thoracotomy, as well as highlight new advances, such as robotic-assisted procedures.

Comparison of right and left ventricular responses to left ventricular assist device support in patients with severe heart failure: a primary role of mechanical unloading underlying reverse remodeling.

BACKGROUND: Left ventricular assist devices (LVAD) reverse ventricular, myocardial, and systemic abnormalities characteristic of severe heart failure (reverse remodeling). The relative contributions of hemodynamic unloading and normalized biochemical milieu to reverse remodeling are unknown. METHODS AND RESULTS: Structural and functional characteristics were measured from 53 hearts of patients undergoing transplantation without LVAD support (medical support) and 33 hearts from patients receiving a median of 46 days of LVAD support (range, 8 to 360 days). Compared with medical support alone, patients receiving LVAD support for >/=30 days had higher central venous pressures (11+/-6 versus 8+/-5 mm Hg, P=0.04), lower pulmonary artery diastolic pressures (14+/-9 versus 21+/-9 mm Hg, P=0.01), and higher cardiac outputs (5.1+/-1.6 versus 3.7+/-1.0 L/min, P<0.001). In LVAD versus transplantation hearts, V(30) (ex vivo volume yielding ventricular pressure of 30 mm Hg) was decreased in the left ventricle (LV) (179+/-75 versus 261+/-118 mL, P=0.005) but not in the right ventricle (RV) (140+/-59 versus 148+/-52 mL, P=NS). LV myocyte diameter decreased more significantly after LVAD support (17%, P=0.05) than in the RV (11%, P=NS). Compared with transplantation, LVAD support increased normalized SERCA2a content in the LV (0.51+/-0.26 versus 1.04+/-0.34, P<0.001) but not in the RV (0.48+/-34 versus 0.67+/-0.55, P=NS). Finally, LVAD support improved force-frequency relations of isolated superfused LV trabeculae (P=0.01) but not RV trabeculae. CONCLUSIONS: Reduction of hemodynamic load is a primary factor underlying several important features of reverse remodeling. These findings do not preclude a possible primary role of neurohormonal factors underlying other facets of reverse remodeling during LVAD support.

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.

Chronic unloading by left ventricular assist device reverses contractile dysfunction and alters gene expression in end-stage heart failure.

BACKGROUND: Left ventricular (LV) assist devices (LVADs) can improve contractile strength and normalize characteristics of the Ca(2+) transient in myocytes isolated from failing human hearts. The purpose of the present study was to determine whether LVAD support also improves contractile strength at different frequencies of contraction (the force-frequency relationship [FFR]) of intact myocardium and alters the expression of genes encoding for proteins involved in Ca(2+) handling. METHODS AND RESULTS: The isometric FFRs of LV trabeculae isolated from 15 patients with end-stage heart failure were compared with those of 7 LVAD-supported patients and demonstrated improved contractile force at 1-Hz stimulation, with reversal of a negative FFR after LVAD implantation. In 20 failing hearts, Northern blot analysis for sarcoplasmic endoreticular Ca(2+)-ATPase subtype 2a (SERCA2a), the ryanodine receptor, and the sarcolemmal Na(+)-Ca(2+) exchanger was performed on LV tissue obtained before and after LVAD implantation. These paired data demonstrated an upregulation of all 3 genes after LVAD support. In tissue obtained from subsets of these patients, Western blot analysis was performed, and oxalate-supported Ca(2+) uptake by isolated sarcoplasmic reticular membranes was determined. Despite higher mRNA for all genes after LVAD support, only SERCA2a protein was increased. Functional significance of increased SERCA2a was confirmed by augmented Ca(2+) uptake by sarcoplasmic reticular membranes isolated from LVAD-supported hearts. CONCLUSIONS: LVAD support can improve contractile strength of intact myocardium and reverse the negative FFR associated with end-stage heart failure. The expression of genes encoding for proteins involved in Ca(2+) cycling is upregulated (reverse molecular remodeling), but only the protein content of SERCA2a is increased.

Disparity of isoflurane effects on left and right ventricular afterload and hydraulic power generation in swine.

UNLABELLED: The interaction between myocardial and vascular effects of anesthetics has a potential impact on how these drugs influence performance of the heart. Most studies have focused on volatile anesthetic effects on the left ventricle (LV) and systemic circulation. Whether the right ventricle (RV) and pulmonary circulation respond in a similar fashion, however, is unclear. In the present study, we therefore examined the dose-related effects of isoflurane on LV and RV contractility and total afterload and related changes to simultaneous effects on the hydraulic power generated by each chamber. Two groups of swine were studied: one received no additional treatment before isoflurane (ISO, n = 6), and the other received hexamethonium, atropine, and propranolol to produce autonomic blockade before isoflurane administration (ISO+AB, n = 4). For each experiment, measurements were made of RV and LV regional segment lengths and pressures, along with proximal aortic and pulmonary arterial (PA) blood flow and pressure during the administration of 0, 0.5, 1.0, and 1.5 minimum alveolar anesthetic concentration (MAC) isoflurane. Contractility was assessed by calculating the regional preload recruitable stroke work slope (PRSW). Afterload was characterized in both nonpulsatile and pulsatile terms by calculating aortic input impedance magnitude (Z). From these data, total arterial resistance (R), characteristic impedance (ZC), and vascular compliance (C) were determined with reference to a three-element Windkessel model of the circulation. Additionally, steady-state (WSS), oscillatory (WOS), and total (WT) hydraulic power output of each ventricle was calculated. In the ISO group, isoflurane produced a nearly threefold greater decrease of peak systolic pressure in the LV than in the RV, yet the dose-related decrease of regional PRSW was virtually the same in both chambers. In the aorta, isoflurane produced a maximal 25% reduction in R at 1.0 MAC and doubled C without a significant change in ZC. Alternatively, PA R was increased from baseline at 1.0 and 1.5 MAC, whereas ZC was increased from all other values at 1.5 MAC. PA C was not altered by isoflurane. In ISO+AB pigs, PA ZC at baseline was higher than that evident in ISO animals but was not altered by isoflurane. In contrast, baseline aortic R was lower in ISO+AB pigs but was still modestly reduced by 1.0 MAC isoflurane. In ISO animals, WT and WSS from both ventricles demonstrated dose-related decreases, but the reductions in LV WTand WSS were greater than those for the RV at all doses. Accordingly, the power requirement per unit flow decreased for the LV but remained constant for the RV. WOS for both ventricles was also reduced by isoflurane. However, the LV WOS to WT ratio increased, which indicates that more power was lost to the system by pulsation. In contrast, reductions in RV WT and WOS were nearly parallel at all isoflurane doses, and the WOS to WT ratio was unchanged. In the ISO+AB group, isoflurane-induced alterations in LV and RV power characteristics were similar to those in the ISO group. These data indicate that, despite similar effects on biventricular contractility, isoflurane exerts qualitatively different effects on RV and LV afterload, in part via alteration in autonomic nervous activity, that influence the distribution of power output between steady-state and pulsatile components. IMPLICATIONS: In this study, we examined the effects of isoflurane on cardiac performance in swine and found that, although the drug depresses contraction of both the left and right ventricles similarly, it has different effects on forces that oppose the ejection of blood. These findings demonstrate that the two interdependent pumps that comprise the heart can be influenced differently by anesthetic drugs.

Nitric oxide synthesis inhibition and right ventricular systolic function in swine.

OBJECTIVES: The present study was designed to evaluate the effects of the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on right ventricular (RV) contractility, both pulsatile and nonpulsatile contributions to afterload, and relate any changes to alterations in performance of the RV as a pump. DESIGN: Prospective drug response. SETTING: University animal laboratory. PARTICIPANTS: Swine. INTERVENTIONS: Six pigs anesthetized with thiopental and fentanyl were instrumented for measurement of RV pressure and pulmonary arterial (PA) pressure, internal diameter, and blood flow. Total RV afterload was calculated as effective PA elastance, with the steady-state component expressed as total arterial resistance, and the pulsatile component assessed by calculation of characteristic impedance and global compliance. The ratio of peak PA flow to RV end-diastolic pressure (RVEDP) was recorded as an index of RV pump function, and the peak ejection rate-of-change of RV power (dPower/dt) was calculated as an index of contractility. In each animal, measurements were obtained before (baseline) and 15 minutes after intravenous injection of 33 mg/kg of L-NAME. MEASUREMENTS AND MAIN RESULTS: Mean PA pressure increased from 14 +/- 3 mmHg at baseline to 23 +/- 6 mmHg after L-NAME, whereas cardiac output, stroke volume, and peak PA flow/RVEDP demonstrated declines and dPower/dt was unchanged. Simultaneously, effective PA elastance increased more than twofold. This increase in total RV afterload was primarily the result of a marked elevation in total arterial resistance (+156%), whereas vascular compliance was reduced by only 30% and characteristic impedance unchanged. CONCLUSIONS: These data indicate that L-NAME produces constriction of resistance vessels within the lung, leading to increased steady-state RV afterload, but had little direct effect on large pulmonary vessels and pulsatile RV load. RV pump performance declines after L-NAME, but contractility is preserved, indicating that the change in systolic performance results primarily from the increase in steady-state afterload.

The dose-dependent effects of halothane on right ventricular contraction pattern and regional inotropy in swine.

The right ventricle (RV) is comprised of two embryologically distinct units, the inflow and outflow tracts, which normally contract sequentially and differ in the magnitude of increased inotropy during sympathetic nervous stimulation. The present study examined the dose-response effects of halothane on the RV contraction pattern and regional contractility in seven open-chest pigs instrumented for measurement of inflow and outflow tract pressures and segment lengths. The RV contraction pattern was evaluated by comparing the phase of inflow and outflow tract shortening, and regional contractility was determined by calculation of preload recruitable stroke work (PRSW) slope. Using this methodology, an inflow-outflow tract contraction phase difference of -27 degrees (inflow tract shortened earlier) was evident at baseline, but was abolished by 1.0 and 1.5 minimum alveolar anesthetic concentration (MAC) halothane; PRSW slope of both the inflow and outflow tracts, however, demonstrated similar dose-related change. To determine whether alterations in cardiac sympathovagal balance played a role in the RV response to halothane, an additional four animals were studied after pretreatment with hexamethonium, propranolol, and atropine. In these animals, there was no difference in the regional contraction phase either at baseline or during halothane administration, and dose-related depression of PRSW by halothane was again similar in both regions. However, when halothane effects on regional PRSW in animals with autonomic blockade were compared to those of neurally intact animals, a 20% greater depression of outflow tract PRSW by 0.5 MAC halothane was evident. This study demonstrates that halothane abolishes the normal sequential pattern of RV contraction without exerting markedly variant negative inotropic effects within different regions of the RV, and provides evidence to suggest that alterations in cardiac sympathovagal balance may contribute to the effect of halothane on RV contraction dynamics.

Effect of halothane on in vivo and in vitro cardiotoxicity of an aminocardenolide.

Halothane opposes cardiotoxicity of neutral-sugar digitalis compounds in intact animals, presumably by depressing a sympathetic component of arrhythmogenesis. However, halothane also produces a dose-related reduction in arrhythmogenicity of ouabain in isolated canine Purkinje fibers, suggesting that the anesthetic may oppose direct mechanisms of cardiotoxicity as well. The present study examined in vivo and in vitro the effect of halothane on the arrhythmogenicity of ASI-222 (3-beta-O[4-amino-4-6-dideoxy-beta-D-galactopyranosyl] digitoxigen in HCl), a highly polar aminocardenolide with no sympathetic component to cardiotoxicity. For in vivo studies, ASI-222 was infused at a rate of 1 microgram/kg/min until appearance of third-degree atrioventricular (AV) block or sustained ventricular arrhythmias in 5 conscious (control) and 6 halothane-anesthetized (1.4% end-tidal) dogs. For in vitro studies, standard microelectrode techniques were used to measure action potentials (AP) in seven excised canine Purkinje fibers superfused with oxygenated Krebs-Henseleit buffer. AP were recorded during control superfusion, after induction of toxicity with 10(-7) M ASI-222, and during exposure to 0.5, 1.0, and 2.0% halothane. Purkinje fibers were paced at 500-ms cycle lengths (CL) for 20 beats, and the amplitude of delayed afterdepolarizations (DAD) were recorded. Pacing at 250 ms CL was used to trigger ectopy. In vivo studies showed no difference in the cardiotoxic dose of ASI-222 between control dogs and those anesthetized with 1.4% halothane. However, in 4 of 6 anesthetized dogs, acutely increasing the inspired halothane concentration suppressed arrhythmias once end-tidal concentration were >2.2%.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of a Doppler pulmonary artery catheter for continuous measurement of right ventricular pump function and contractility during single lung transplantation.

Despite numerous technologic advances in intraoperative monitoring, the only methods routinely available for assessment of right ventricular function in lung transplant recipients are continuous measurement of right heart pressures and intermittent thermodilution determination of cardiac output and ejection fraction. Additional data may now be obtained with transesophageal echocardiography, although this technology is expensive and not widely available and requires diverting attention from a potentially unstable patient for data acquisition and analysis. Recently, a Doppler pulmonary artery catheter was introduced that measures beat-to-beat pulmonary artery blood flow-velocity, cross sectional area, and volume flow. Because of data indicating that acceleration of blood in the pulmonary artery (measured as the first derivative of either the velocity or flow waveform) is a sensitive indicator of right ventricular contractility, we have used waveforms obtained with the catheter for assessment of right ventricular pump function (stroke volume and peak pulmonary artery flow rate) and contractility in heart surgery patients. We report here our experience with this method in two patients undergoing left single lung transplantation.

Comparison of cardiac output measured by intrapulmonary artery Doppler, thermodilution, and electromagnetometry.

A Doppler pulmonary artery catheter system (Doppler cardiac output monitor or DOPCOM) that continuously measures instantaneous and mean cardiac output was recently introduced. Because thermodilution (TD) flow measurements may not represent an adequate standard, the present study was designed to compare TD and DOPCOM cardiac output measurements with aortic electromagnetic (EM) flow in cardiac surgical patients. Twenty-one patients scheduled for elective coronary artery bypass grafting were enrolled in the study. Simultaneous measurement of cardiac output by all three methods was performed before cardiopulmonary bypass, after cardiopulmonary bypass with the aorta cannulated and volume intermittently infused, and after decannulation. Analysis of all data demonstrated fair TD and EM correlation (r = 0.80), with minimal bias (0.03 +/- 1.21 L/min) and a median absolute error of 0.53 L/min; DOPCOM and EM data showed moderate correlation (r = 0.64), a bias of -0.61 +/- 1.50 L/min, and a median absolute error the same as TD (0.51 L/min). However, distribution of DOPCOM values was heavily skewed by 3 patients in whom flow measurements immediately after cardiopulmonary bypass were markedly different between the DOPCOM and electromagnetometry, probably because of malposition of the Doppler transducers secondary to partial catheter withdrawal during bypass. Consistent with this theory was the finding that before CPB, the DOPCOM was significantly better than TD in predicting EM flow (median absolute error: DOPCOM, 0.12 L/min, and TD, 0.48 L/min; p = 0.04). Our data suggest that, in general, the DOPCOM shows similar precision to TD for predicting EM flow measurements, although the DOPCOM may underestimate actual flow.(ABSTRACT TRUNCATED AT 250 WORDS)

The rational pharmacology of digoxin.

Although digoxin remains one of the most widely prescribed drugs in the United States, potential pharmacodynamic and pharmacokinetic interactions between this compound and other drugs, diseases, and events commonly encountered in the perioperative period remain largely unappreciated. Furthermore, the therapeutic benefit of discontinuing or initiating digoxin treatment preoperatively remains unclear. We present a basic review of current knowledge regarding digoxin pharmacology and examine those concepts from the perspective of clinical anesthesiologists.

Inaccuracy of cardiac output by thermodilution during acute tricuspid regurgitation.

We have been comparing cardiac output measured with a novel Doppler pulmonary artery catheter to that measured by thermodilution and aortic electromagnetometry in cardiac surgical patients. We report here our observation of a nearly twofold increase in thermodilution cardiac output after the acute intraoperative onset of tricuspid regurgitation that was not confirmed by the novel catheter or direct measurement of aortic blood flow. We conclude that in some patients, acute tricuspid regurgitation may lessen the reliability of thermodilution cardiac output.

The cardiovascular response to digoxin in conscious dogs with left atrial obstruction.

In addition to positive inotropic and atrioventricular conduction-blocking properties, digoxin is capable of producing systemic and pulmonary vasoconstriction. However, whether chronic digoxin treatment exacerbates the pulmonary hypertension that results from left atrial (LA) outflow obstruction has not been specifically examined. This study assessed the vascular and inotropic responses to 5 days of digoxin treatment in six conscious dogs before and after filling a permanently implanted LA balloon. Dogs were also instrumented to measure left ventricular (LV) pressure, LV dP/dt, mean systemic arterial (MAP), right atrial (RAP), pulmonary arterial, and pulmonary capillary wedge pressures, as well as cardiac output (CO). Under normal conditions with the balloon empty, digoxin treatment (40 micrograms/kg loading dose and 12 micrograms/kg/d for 5 days) reduced CO (-17%) and increased systemic (SVR) and pulmonary (PVR) vascular resistances 27% and 37%, respectively; heart rate (HR) and LV dP/dt were not changed. Filling the balloon with enough saline to double PVR also increased SVR (52%), HR (42%), and RAP (92%), and reduced CO (-24%). During LA outflow obstruction, 5 days of digoxin reduced HR (-17%), SVR (-29%), and RAP (-23%), but did not alter PVR, CO, or LV dP/dt. This study demonstrates that although systemic and pulmonary vasoconstriction result from chronic digoxin treatment under normal conditions, the drug produces systemic vasodilation and no change in PVR during LA outflow obstruction.

Prostaglandin E1 and intrapulmonary shunt in cardiac surgical patients with pulmonary hypertension.

Unlike many other vasodilators, prostaglandin E1 may reduce pulmonary vascular resistance without changing intrapulmonary shunt in patients with adult respiratory distress syndrome. Whether the same is true for surgical patients with cardiogenic pulmonary hypertension but normal gas exchange remains unclear. Data from the intraoperative records of 8 patients with pulmonary hypertension and elevated pulmonary vascular resistance were used for the study. Hemodynamic variables had been monitored through radial arterial cannulas and pulmonary arterial catheters. Arterial and mixed venous oxygen tension, carbon dioxide tension, oxygen saturation, and hemoglobin level, as well as cardiac output and pulmonary capillary wedge pressure, had been determined in each patient before prostaglandin E1 infusion was started and again when the desired pulmonary vascular response had been achieved. Pulmonary and systemic vascular resistances and intrapulmonary shunt were calculated from standard formulas. Infusion rates of prostaglandin E1 ranged from 7 to 135 ng/kg/min. Prostaglandin E1 reduced mean pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary capillary wedge pressure but did not change intrapulmonary shunt. Heart rate and mean arterial and right atrial pressures were not changed, whereas systemic vascular resistance decreased and cardiac output increased. The present study shows that prostaglandin E1 reduces pulmonary arterial pressure and pulmonary vascular resistance without dramatic changes in intrapulmonary shunt in patients with pulmonary hypertension secondary to cardiac disease.