Vasoplegic syndrome after cardiovascular surgery: A review of pathophysiology and outcome-oriented therapeutic management.

BACKGROUND: Vasoplegic syndrome (VPS) is defined as systemic hypotension due to profound vasodilatation and loss of systemic vascular resistance (SVR), despite normal or increased cardiac index, and characterized by inadequate response to standard doses of vasopressors, and increased morbidity and mortality. It occurs in 9%-44% of cardiac surgery patients after cardiopulmonary bypass (CPB). The underlying pathophysiology following CPB consists of resistance to vasopressors (inactivation of Ca2+ voltage gated channels) on the one hand and excessive activation of vasodilators (SIRS, iNOS, and low AVP) on the other. Use of angiotensin-converting enzyme inhibitor (ACE-I), calcium channel blockers, amiodarone, heparin, low cardiac reserve (EF < 35%), symptomatic congestive heart failure, and diabetes mellitus are the perioperative risk factors for VPS after cardiac surgery in adults. Till date, there is no consensus about the outcome-oriented therapeutic management of VPS. Vasopressors such as norepinephrine (NE; 0.025-0.2 µg/kg/min) and vasopressin (0.06 U/min or 6 U/h median dose) are the first choice for the treatment. The adjuvant therapy (hydrocortisone, calcium, vitamin C, and thiamine) and rescue therapy (methylene blue [MB] and hydroxocobalamin) are also considered when perfusion goals (meanarterial pressure [MAP] > 60-70 mmHg) are not achieved with nor-epinephrine and/or vasopressin. AIMS: The aims of this systematic review are to collect all the clinically relevant data to describe the VPS, its potential risk factors, pathophysiology after CPB, and to assess the efficacy, safety, and outcome of the therapeutic management with catecholamine and non-catecholamine vasopressors employed for refractory vasoplegia after cardiac surgery. Also, to elucidate the current and practical approach for management of VPS after cardiac surgery. MATERIAL AND METHODS: "PubMed," "Google," and "Medline" weresearched, and over 150 recent relevant articles including RCTs, clinical studies, meta-analysis, reviews, case reports, case series and Cochrane data were analyzed for this systematic review. The filter was applied specificallyusing key words like VPS after cardiac surgery, perioperative VPS following CPB, morbidity, and mortality in VPS after cardiac surgery, vasopressors for VPS that improve outcomes, VPS after valve surgery, VPS after CABG surgery, VPS following complex congenital cardiac anomalies corrective surgery, rescue therapy for VPS, adjuvant therapy for VPS, definition of VPS, outcome in VPS after cardiac surgery, etiopathology of VPS following CPB. This review did not require any ethical approval or consent from the patients. RESULTS: Despite the recent advances in therapy, the mortality remains as high as 30%-50%. NE has been recommended the most frequent used vasopressor for VPS. It restores and maintain the MAP and provides the outcome benefits. Vasopressin rescue therapy is an alternative approach, if catecholamines and fluid infusions fail to improve hemodynamics. It effectively increases vascular tone and lowers CO, and significantly decreases the 30 days mortality. Hence, suggested a first-line vasopressor agent in postcardiac surgery VPS. Terlipressin (1.3µg/kg/h), a longer acting and more specific vasoconstrictor prevents the development of VPS after CPB in patients treated with ACE-I. MB significantly reduces morbidity and mortality of VPS. The Preoperative MB (1%, 2mg/kg/30min, 1h before surgery) administration in high risk (on ACE-I) patients for VPS undergoing CABG surgery, provides 100% protection against VPS, and early of MB significantly reduces operative mortality, and recommended as a rescue therapy for VPS. Hydroxocobalamin (5 g) has been recommended as a rescue agent in VPS refractory to multiple vasopressors. A combination of ascorbic acid (6 g), hydrocortisone (200 mg/day), and thiamine (400 mg/day) as an adjuvant therapy significantly reduces the vasopressors requirement, and provides mortality and morbidity benefits. CONCLUSION: Currently, the VPS is frequently encountered (9%-40%) in cardiac surgical patients with predisposing patient-specific risk factors and combined with inflammatory response to CPB. Multidrug therapy (NE, MB, AVP, ATII, terlipressin, hydroxocobalamin) targeting multiple receptor systems is recommended in refractory VPS. A combination of high dosage of ascorbic acid, hydrocortisone and thiamine has been used successfully as adjunctive therapyto restore the MAP. We also advocate for the early use of multiagent vasopressors therapy and catecholamine sparing adjunctive agents to restore the systemic perfusion pressure with a goal of preventing the progressive refractory VPS.

Evaluation of different types of inferior vena cava cannulae placement by transesophageal echocardiography and its impact on hepatic dysfunction.

BACKGROUND: Postoperative hepatic dysfunction may occur in an otherwise uncomplicated open heart surgery. One of the reasons is malpositioning of the inferior vena cava (IVC) cannula in the hepatic vein (HV) or beyond. A straight cannula is considered more likely to be malpositioned compared to the angled cannula and a malpositioned cannula can lead to hepatic dysfunction. METHODS: In this prospective study, forty adult patients undergoing atrial septal defect repair were randomized into two groups as: straight cannula group (n=20) and angled cannula group (n=20). The cannula position was assessed by transesophageal echocardiography (TEE) (hepatic vein view). Alanine aminotransferase levels (ALT) and bilirubin levels were measured immediately, at 6 hours and on day 1, day 2 and day 7 after surgery as a marker of hepatic injury. RESULTS: TEE localization of the IVC cannula was achieved in all patients except one. Visualization was good in 85% of patients. A cannula in the HV or beyond the HV in the IVC was considered malpositioned. The number of cases of cannula malposition was 10 (50%) and 4 (20%) in the straight and angled cannula groups, respectively. The pattern of change in serum bilirubin and liver enzymes levels in the postoperative period was similar in both the groups (p>0.05). The mean distance between the right atrium (RA) - inferior vena cava (IVC) junction to the hepatic vein was 1.94±0.56 cm and the mean diameters of the IVC and HV were 1.95±0.5 and 1.31±0.33 cm, respectively. CONCLUSION: TEE can be used to monitor IVC cannula position. A higher frequency of cannula malposition was observed with the straight cannula compared to the angled cannula, but was not found to be associated with hepatic dysfunction.

Systemic and local levels of fetuin-a in calcified mitral valves of rheumatic heart disease.

BACKGROUND AND AIM OF THE STUDY: Fetuin-A is a circulating glycoprotein that inhibits ectopic calcification. The study aim was first, to assess serum fetuin-A level in patients with calcified rheumatic mitral valve disease (RMVD), and second, to demonstrate the presence of fetuin-A by immunohistochemistry (IHC) in calcified RMVD which, to date, has not been verified in other studies. METHODS: The study group comprised 68 adult patients with isolated RMVD and normal renal function. Of these patients, 34 (27 males, seven females; mean age 33.44 +/- 9.0 years) had severe calcification (Wilkins calcium score 3 or 4) and 34 (25 males, nine females; mean age 30.8 +/- 8.5 years) had mild calcification (Wilkins calcium score 1 or 2). A group of 32 age- and gender-matched healthy subjects (25 males, seven females; mean age 29.5 +/- 4.6 years) served as controls. Baseline serum fetuin-A levels were measured using an enzyme-linked immunosorbent assay (ELISA), while Wilkins calcium scores were assessed using either transthoracic or transesophageal echocardiography. Serum levels of calcium, phosphorus and alkaline phosphatase were assessed in all subjects. Histopathological examinations of ten severely calcific rheumatic mitral valves were made and compared with 10 non-calcified rheumatic mitral valves, all of which had undergone mitral valve replacement. RESULTS: Serum fetuin-A levels were significantly lower in RMVD patients than in controls (108.83 +/- 7.1 versus 114.46 +/- 3.32 ng/ml; p = 0.014). However, there was no significant difference in fetuin-A level between patients with severe (C3/C4) versus mild calcification (C1/C2) (108.84 +/- 7.82 versus 108.82 +/- 6.36 ng/ml; p = NS). No correlation of fetuin-A was seen with serum high-sensitivity C-reactive protein, calcium, phosphorus and alkaline phosphatase, or with Wilkins' calcium score. IHC analyses revealed the presence of fetuin-A in the mesenchymal matrix and calcified area of calcific valves, while minimal to absent fetuin-A deposition was detected in the mesenchymal matrix of non-calcified mitral valves. CONCLUSION: Serum fetuin-A levels were significantly decreased in patients with calcific RMVD. The present study was the first to demonstrate fetuin-A in the calcified mitral valve of rheumatic etiology, and suggests its possible role in the pathophysiology of calcific mitral valve disease. Further studies are required, however, to determine therapeutic implications.

Role of magnesium alone or in combination with diltiazem and/or amiodarone in prevention of atrial fibrillation following off-pump coronary artery bypass grafting.

Objectives: In this study the authors have tried to examine the role of magnesium alone or in combination with diltiazem and / or amiodarone in prevention of atrial fibrillation (AF) following off-pump coronary artery bypass grafting (CABG). Background: AF after CABG is common and contributes to morbidity and mortality. Various pharmacological preventive measures including magnesium, amiodarone, diltiazem, and combination therapy among others have been tried to lower the incidence of AF. Most of the studies have been performed in patients undergoing conventional on-pump CABG. In this uncontrolled trial, efficacy of magnesium alone or in combination with amiodarone and / or diltiazem has been studied in patients undergoing off-pump CABG. Methods: One hundred and fifty patients undergoing off-pump CABG were divided into 3 groups, Group M (n=21) received intraoperative magnesium infusion at 30mg/ kg over 1 hour after midline sternotomy; Group MD (n=78) received magnesium infusion in similar manner with diltiazem infusion at 0.05 µg/kg/hr throughout the intraoperative period; Group AMD (n=51) received preoperative oral amiodarone at a dose of 200 mg three times a day for 3 days followed by 200 mg twice daily for another 3 days followed by 200 mg once daily till the day of surgery along with magnesium and diltiazem infusion as in other groups. AF lasting more than 10 min or requiring medical intervention was considered as AF. Results: The overall incidence of postoperative AF was 12.6% with 11.7% in group AMD, 19% in group M, and 11.5% in group MD, which was not statistically significant. Conclusions: It is concluded that the use of amiodarone and/or diltiazem in addition to magnesium did not result in additional benefit of lowering the incidence of AF.

Delayed presentation of iatrogenic left ventricular pseudoaneurysm.

Occurrence of left ventricular aneurysm outside the realm of ischemic heart disease is uncommon and one following an iatrogenic trauma is very rare. We describe one such case of left ventricular pseudoaneurysm developing following pericardiocentesis and presenting one year after the procedure, and its successful surgical management.

Spontaneous bag mask ventilation for establishing cardiopulmonary bypass via mid-sternotomy in patients with severe tracheal stenosis: A series of three patients.

In patients with critical tracheal stenosis, particularly involving the lower part of trachea, a highly experienced team of anesthesiologists to tackle the difficulties of securing and maintaining the ventilation, cardiac surgeon who can swiftly establish cardiopulmonary bypass, an experienced surgeon for tracheal reconstruction are a prerequisite for managing these highly complex cases. The present paper describes three patients suffering from severe tracheal narrowing wherein spontaneous bag-mask ventilation was used for establishing cardiopulmonary bypass via mid-sternotomy as a rare life-saving procedure for urgent tracheal reconstructive surgery. A highly experienced team of anesthesiologists to tackle the difficulties of securing and maintaining the ventilation, cardiac surgeon who can swiftly establish CPB, and an experienced surgeon for tracheal reconstruction are a prerequisite for managing these highly complex cases. The present paper describes three patients suffering from severe tracheal narrowing wherein spontaneous bag-mask ventilation was used for establishing CPB via mid-sternotomy as a rare life-saving procedure for urgent tracheal reconstructive surgery.

Atrial ECG as a guide to the placement of central venous catheter in patients undergoing Open Heart Surgery.

Hundred adults undergoing open heart surgery were randomized into two equal groups. In group I (n=50), surface anatomical landmarks and in group II (n=50) atrial ECG was used as a guide for correct placement of the central venous catheter (within 1 cm of superior vena cava - right atrial junction). The position of the catheter tip was confirmed by direct palpation by the surgeon on the operating table and by radiological examination in the post operative period. Surgeon's assessment revealed that the catheter was successfully placed in 32 (69.6%) patients in group II and 25 (50%) patients in group I (p=NS). Radiological examination revealed that the catheter was successfully placed in 31 (67.4%) patients in group II and in 28 (57.1%) patients in group I (p=NS). Amongst the unsuccessful placements right atrial placement was present in 5 patients (10%) in group I and 7 patients (15.2%) in group II by surgeon's assessment and 8 patients (16.3%) in group I and 9 patients (9.6%) in group II by radiological examination (p=NS) No complications related to intracardiac placement occurred in any of the patients. We conclude that atrial ECG is a promising technique for central venous catheter placement, although it did not significantly increase the correct placement in this study. This may be due to alteration in the relationship of sino-atrial node and superior vena cava - right atrial junction in patients with cardiac disease. Further studies defining the correct technique of insertion, (especially in cardiac patients) are necessary to improve the success rate.