Olav F.M. Sellevold

Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery

The American College of Cardiology, American Heart Association, and the European Society of Cardiology are all in the process of completing updated versions of our Guidelines for Perioperative Care. Our respective writing committees are undertaking a careful analysis of all relevant validated studies and always incorporate appropriate new trials and meta-analyses into our evidence review. In the interim, our current joint position is that the initiation of beta blockers in patients who will undergo non-cardiac surgery should not be considered routine, but should be considered carefully by each patients treating physician on a case-by-case basis. Please see the expression of concern which is free to view in Eur Heart J (2013) 34 (44): 3460; doi: 10.1093/eurheartj/eht431. AAA : abdominal aortic aneurysm ACC : American College of Cardiology ACE : angiotensin-converting enzyme ACS : acute coronary syndrome AHA : American Heart Association AR : aortic regurgitation ARB : angiotensin receptor blocker AS : aortic stenosis AF : atrial fibrillation BBSA : β-blocker in spinal anaesthesia BNP : brain natriuretic peptide CABG : coronary artery bypass grafting CARP : coronary artery revascularization prophylaxis CASS : coronary artery surgery study CI : confidence interval COX-2 : cyclooxygenase-2 COPD : chronic obstructive pulmonary disease CPET : cardiopulmonary exercise testing CPG : Committee for Practice Guidelines CRP : C-reactive protein CT : computed tomography cTnI : cardiac troponin I cTnT : cardiac troponin T CVD : cardiovascular disease DECREASE : Dutch Echocardiographic Cardiac Risk Evaluating Applying Stress Echo DES : drug-eluting stent DIPOM : Diabetes Postoperative Mortality and Morbidity DSE : dobutamine stress echocardiography ECG : electrocardiography ESC : European Society of Cardiology FEV1 : forced expiratory volume in 1 s FRISC : fast revascularization in instability in coronary disease HR : hazard ratio ICU : intensive care unit IHD : ischaemic heart disease INR : international normalized ratio LMWH : low molecular weight heparin LQTS : long QT syndrome LR : likelihood ratio LV : left ventricular MaVS : metoprolol after surgery MET : metabolic equivalent MI : myocardial infarction MR : mitral regurgitation MRI : magnetic resonance imaging MS : mitral stenosis NICE-SUGAR : normoglycaemia in intensive care evaluation and survival using glucose algorithm regulation NSTEMI : non-ST-segment elevation myocardial infarction NT-proBNP : N-terminal pro-brain natriuretic peptide NYHA : New York Heart Association OPUS : orbofiban in patients with unstable coronary syndromes OR : odds ratio PaCO2 : mixed expired volume of alveolar and dead space gas PAH : pulmonary arterial hypertension PETCO2 : end-tidal expiratory CO2 pressure PCI : percutaneous coronary intervention PDA : personal digital assistant POISE : PeriOperative ISchaemic Evaluation trial QUO-VADIS : QUinapril On Vascular ACE and Determinants of ISchemia ROC : receiver operating characteristic SD : standard deviation SMVT : sustained monomorphic ventricular tachycardia SPECT : single photon emission computed tomography SPVT : sustained polymorphic ventricular tachycardia STEMI : ST-segment elevation myocardial infarction SVT : supraventricular tachycardia SYNTAX : synergy between percutaneous coronary intervention with taxus and cardiac surgery TACTICS : treat angina with aggrastat and determine cost of therapy with an invasive or conservative strategy TIA : transient ischaemic attack TIMI : thrombolysis in myocardial infarction TOE : transoesophageal echocardiography UFH : unfractionated heparin VCO2 : carbon dioxide production VE : minute ventilation VHD : valvular heart disease VKA : vitamin K antagonist VO2 : oxygen consumption VPB : ventricular premature beat VT : ventricular tachycardia Guidelines and Expert Consensus Documents aim to present management and recommendations based on the relevant evidence on a particular subject in order to help physicians to select the best possible management strategies for the individual patient suffering from a specific condition, taking into account not only the impact on outcome, but also the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks. The legal implications of medical guidelines have been discussed previously.1 A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) and also by other organizations or related societies. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC guidelines and Expert Consensus Documents can be found on the ESC website in the guidelines section (www.escardio.org). In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. …

High performance liquid chromatography: a rapid isocratic method for determination of creatine compounds and adenine nucleotides in myocardial tissue

Previous methods for high performance liquid chromatography (HPLC) measurements of myocardial high energy phosphate (HEP) compounds have used either two different assays or a gradient technique in order to determine both creatine compounds (creatine (Cr), creatine phosphate (CrP)), and adenine nucleotides (ATP, ADP, AMP). An isocratic ion-pair reversed-phase assay has been developed which allows for the rapid (single run within 10 min) measurement of these compounds in extracts from freeze-clamped and freeze-dried myocardial tissue. The HPLC system made use of a RP18 column and a spectrophotometer, set at 206 nm. The mobile phase consisted of KH2PO4 (215 mM), tetrabutylammonium hydrogen sulphate (2.3 mM) and acetonitrile (3.5%) at pH 6.25. A distinct separation (confirmed by enzymatic and other methods) of HEP compounds was achieved. Standard curves were linear and passed through the origo for all examined concentrations. In isolated rat hearts subjected to control aerobic perfusion the following values were obtained (mumol/g dry wt, mean +/- S.E.M.): ATP 26.6 +/- 0.4, ADP 4.6 +/- 0.1, AMP 1.4 +/- 0.1, CrP 35.5 +/- 1.0, Cr 46.2 +/- 1.1. Values for HEP compounds of hearts undergoing anoxia +/- reoxygenation, and ischemia +/- reperfusion are presented. The importance of the procedure for extraction of HEP from freeze-dried cardiac tissue is highlighted.

GUIDELINES FOR PRE-OPERATIVE CARDIAC RISK ASSESSMENT AND PERIOPERATIVE CARDIAC MANAGEMENT IN NON-CARDIAC SURGERY

Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery.

Epidural Morphine for Postoperative Pain: Experience with 1085 Patients

A prospective study of the effect and side‐effects of epidural morphine for pain relief in 1085 patients after thoracic, abdominal, urologic, or orthopaedic surgery was performed. Morphine chloride was diluted in saline or bupivacaine and administered through an epidural catheter placed at a segmental level appropriate for the type of surgery. The initial dose was 4 or 6 mg morphine and supplementary doses were given when needed to obtain complete freedom from pain during deep breathing or nursing care. The total dose of epidural morphine from end of surgery until the next morning varied from 4 to 18 mg. 97% of hip arthroplasty patients, 91% of prostatectomy patients and thoracotomy patients, 90% of patients after major lower extremity surgery and 88% of patients after laparotomy were completely satisfied with the postoperativr course. For hip arthroplasty and major extremity surgery, an initial dose of 4 mg of epidural morphine was as effective as 6 mg. After prostatectomy, laparotomy, and thoracotomy, an initial dose of 6 mg gave significantly better effect than 4 mg. Pruritus occurred in 11%, nausea or vomiting in 34%, and respiratory depression in 0.9% of the total patient population. Urinary retention occurred in 42% of patients not having urinary catheters in place. Postoperative nausea or vomiting was more frrquent in women than in men (P<0.001). There was a higher incidence of nausea or vomiting in men experiencing pain than in men who were completely pain‐free after abdominal surgery (P<0.001). Respiratory depression was rare and occurred as a gradually decreasing respiratory rate. Treatment with naloxone was effective without pain‐breakthrough. Naloxone relieved pruritus in 9O% of patients in whom it was attempted, but was not effective in treating nausea, vomiting, or urinary retention. After this study our dosage regimen for postoperative epidural morphine is: for major surgery of the lower limb or hip arthroplasty 4 mg; after prostatectomy. laparotomy, and thoracotomy 6 mg. No later than 12 h before the patients leave the postoperative care unit, half the initial dose of epidural morphine is usually repeated. Morphine is diluted in bupivacaine if pain is already present, otherwise in saline.

Is atrial fibrillation caused by extracorporeal circulation

BACKGROUND Atrial fibrillation is the most common rhythm disturbance encountered after open heart operations, with a reported incidence up to 40%. Despite its high incidence and clinical relevance its etiology remains obscure. It has been hypothesized that atrial fibrillation might be related to extracorporeal circulation. We performed a retrospective study (January 1, 1997 to December 31, 1997) comparing the incidence of atrial fibrillation in 3 groups of patients revascularized with and without extracorporeal circulation. METHODS The first group comprised patients with coronary artery disease operated on with standard revascularization technique with cardiopulmonary bypass (n = 685). The second group included patients who had minimally invasive coronary artery bypass grafting without the use of extracorporeal circulation (n = 19). Patients in the third group had off-pump transmyocardial laser revascularization (n = 19). RESULTS There was no significant difference in the incidence of atrial fibrillation in the group that had conventional coronary artery bypass and the group that had minimally invasive coronary artery bypass without cardiopulmonary bypass. The incidence of atrial fibrillation was significantly lower in the transmyocardial laser group compared with the other two groups. CONCLUSIONS The present study found that postoperative atrial fibrillation is not caused solely by extracorporeal circulation, but patients who had transmyocardial laser revascularization had a significantly lower incidence of atrial fibrillation.

Guiding Surgical Cannulation of the Inferior Vena Cava with Transesophageal Echocardiography

We studied 150 adult cardiac surgery patients to assess visualization of the venous cannula and the venous system by intraoperative transesophageal echocardiography and to register the incidence of cannulation of hepatic veins. The quality of images, the dimensions of the venous system, the position of the venous cannula, and the adequacy of venous return were registered. Acceptable image quality of the inferior vena cava and the right hepatic vein (RHV) was obtained in 95% and 87% of cases, respectively. Considerable individual variations were found in the dimensions of the venous system. The cannula position could be determined in 99% of the cases. Ten percent of venous cannulae were primarily placed in the RHV. A short distance between the eustachian valve and the RHV possibly predisposes to cannulation of the RHV. No other patient-related factors were associated with cannula position. Placement of the cannula deep in the inferior vena cava was associated with reduced venous return and may be a more important cause of reduced return than a cannula positioned in a hepatic vein.

Heparin–coated circuit during cardiopulmonary bypass

A prospective randomized study was performed to investigate the effect of surface coating with covalently endpoint–attached heparin (Carmeda Bio Active Surface) and reduced general heparinization on haematological indices and complement C5 activation. Care was taken to optimize the rheological design of the system using centrifugal pump and a closed system without venting or machine suction. Twenty patients scheduled for aortocoronary bypass grafting (EF > 0.5) participated in the study. Ten patients were randomized to be treated with heparin–coated equipment (CBAS) and reduced i.v. heparin (1.5 mg kg‐1) while 10 patients treated with identical but noncoated equipment and full heparinization (3 mg–kg‐1) served in a Control group. A vacuum suction was used to collect the blood from the operating field and it was autotransfused at weaning from extracorporeal circulation (ECC). Blood samples were obtained from the venous (precircuit) and arterial (postcircuit) side. We used a new and very specific method for detection of C5a based on monoclonal antibodies. The concentration of C5a was low in both groups during the operation but a significant increase was seen on days 1 and 2. In the Control group there was an increase from 10.2 ngml‐1±1.2 to 27.5 ng ml‐1 ± 4.8 on day 2 and in the CBAS group from 10.7 ng ml‐1 ± 1.2 to 35.6 ng ml‐1 ± 11.6 on day 2 (NS between groups). The granulocytes and total leukocyte count increased at the end of ECC and was maintained at the elevated level throughout the study period. The amount of free haemoglobin was high in the autotransfused blood in both groups. The present results confirm the feasibility of reducing general heparin when using heparin–coated systems but the study does not support the superiority of such coating with regard to biocompatibility in short procedures with a Theologically optimized circuit. The potential benefit from reduced heparin and protamine has not been fully evaluated.

The calcium paradox phenomenon: a flow rate and volume response study of calcium-free perfusion.

A dose-response study concerning the importance of the flow rate (0.5 to 12 ml/min) and volume (2.5 to 60 ml) of calcium-free coronary perfusion (duration 5 min) in the induction of a calcium paradox on reperfusion (duration 15 min) with calcium-containing medium has been performed in the isolated rat heart (37 degrees C). On the basis of enzymatic, physiological, and metabolic assessments three different levels of tissue injury were identified: a minimal paradox at 1.0 ml/min or 5 ml, a subtotal paradox at 2 ml/min or 10 ml and a total paradox at 9 ml/min or 45 ml. Ultrastructural examination revealed that cellular injury following calcium repletion was always severe, and that an increase in the flow rate and volume of calcium-free perfusion increased the number of severely injured cells. During calcium-free perfusion the external lamina largely remained intact over the surface coat of the sarcolemma, but variable degrees of separation of intercalated discs were observed. It is concluded that the calcium paradox model of myocardial injury presents a rather sharp threshold related to the flow rate or volume of calcium-free coronary perfusion and that on trespassing this threshold there is a narrow zone characterized by a decreasing number of viable cells. Furthermore, the study indicates that a separation of the external lamina from the surface coat of the sarcolemma is not a prerequisite for the induction of a calcium paradox, and that cell injury may occur in the presence of intact intercalated discs.

Markers for Endothelial Activation During Open Heart Surgery

BACKGROUND Reliable markers for endothelial activation are needed when studying biocompatibility of cardiopulmonary bypass. METHODS Blood samples from 21 patients undergoing combined valve and coronary artery bypass surgery were collected before anesthesia (T1), after re-transfusion of blood from the heart-lung machine (T2), and on the first postoperative morning (T3). Concentrations of soluble markers were determined using sandwich enzyme-linked immunoadsorbent assay for sICAM-1, sVCAM-1, and sE-selectin. The sera were also used to stimulate human umbilical vein endothelial cells (HUVEC) in culture for 6 hours, in which activation was measured using cell enzyme immunoassay for mICAM-1 and mVCAM-1. RESULTS The concentrations of sICAM-1 and sVCAM-1 increased during both measurement intervals (p < 0.05). The sICAM-1 T1 was 311.0 ng/mL (range, 271.0 to 350.7 ng/mL); the sICAM-1 T2 was 341.6 ng/mL (range, 322.0 to 422.0 ng/mL), and the sICAM-1 T3 was 400.2 ng/mL (range, 348.0 to 556.4 ng/mL; the sVCAM-1 T1 was 607.5 ng/mL (range, 497.8 to 813.8 ng/mL), the sVCAM-1 T2 was 755.3 ng/mL (range, 660.6 to 834.4 ng/mL), and the sVCAM-1 T3 was 1149.0 ng/mL (946.0 to 1406.0 ng/mL); whereas the sE-selectin increased from T1 to T3 (p < 0.01). Both the mICAM-1 (p < 0.002) and the mVCAM-1 (p < 0.005) increased on the human umbilical vein endothelial cells in culture after stimulation with the patient sera. The amounts of soluble markers in vivo were not correlated with the degree of endothelial activation in vitro, but were correlated with various operative variables including age, medication, and time of aortic cross-clamping. CONCLUSIONS Endothelial cells were activated during cardiopulmonary bypass. The soluble adhesion molecules sICAM-1, sVCAM-1, and sE-selectin displayed different kinetics, rendering it difficult to determine a simple expression for the degree of endothelial cell activation. Clinically, sVCAM-1 seemed to be the best-suited marker for endothelial cell activation, because it was only associated with aortic cross-clamping and heparin and protamine doses, and it also showed the largest numerical changes.

The marked reduction in mixed venous oxygen saturation during early mobilization after cardiac surgery: the effect of posture or exercise?

Early mobilization after cardiac surgery induces a marked reduction in mixed venous oxygen saturation (Svo2). Using pulmonary artery catheters and indirect calorimetry, we investigated the effects of exercise and postural change on cardiac index (CI) and Svo2 before and on the first morning after coronary artery bypass surgery. Sixteen patients with an ejection fraction >0.50 were studied at rest, during supine bicycle exercise, and during passive standing. Supine cycling at 30 W increased CI by 1.5 ± 0.8 L · min−1 · m−2 before and 0.9 ± 0.7 L · min−1 · m−2 after surgery (P < 0.05), whereas Svo2 was reduced from 80% ± 4% at rest to 63 ± 6% preoperatively (P < 0.05) and from 71% ± 5% to 46% ± 11% postoperatively (P < 0.05). Passive standing reduced CI by 0.8 ± 0.5 L · min−1 · m−2 before and 0.3 ± 0.4 L · min−1 · m−2 after surgery (P < 0.05). Svo2 was reduced from 79% ± 5% to 64% ± 7% preoperatively (P < 0.05) and from 72% ± 6% to 60% ± 6% postoperatively (P < 0.05). The exercise challenge revealed an altered cardiovascular response after surgery, causing a larger reduction in Svo2 for the same workload. Passive standing significantly reduced Svo2 both days, but this effect was less pronounced after surgery. The response to postural change and exercise was altered after surgery and may both contribute to the reduction in Svo2 during postoperative mobilization.