Dept Of Anesthesiology & Critical Care, University Of Pennsylvania School Of Medicine

The Frank Murphy Memorial Lecture 2008 - Fontan Physiology

This is a continuation of Dr. Cripes comments concerning adult congenital heart disease:

Fontan physiology represents a unique set of circumstances in cardiac performance.  This circulation is often associated with CHD, but may be seen in other cardiac pathology.  The primary situation occurring, regardless if it is a result of a congenital malformation of the heart or massive RV dysfunction, is the loss of a traditional right sided pumping mechanism.  The return of systemic venous blood is directed passively into the pulmonary circulation.  There is no RV to pump blood.  In Fontan physiology pulmonary blood flow and cardiac output are dependent on a transpulmonary gradient (TPG).  The TPG may be used as a guide to gage the forward flow of blood in the pulmonary circulation.  The TPG is estimated by taking the CVP minus the LVEDP (PCWP if using a Swan-Ganz catheter).  An ideal TPG is approximately 5-8 mmHg. 

            Goals in caring for patients with Fontan physiology may be broken down into pre-pulmonary/cardiac, pulmonary and cardiac.  The pre-pulmonary/cardiac goals in Fontan physiology include the presence of an unobstructed venous return to pulmonary circulation.  The importance of an adequate preload cannot be overemphasized.  These patients are exquisitely preload sensitive.  The patient needs widely patent anastomotic connections in the case of a surgically corrected CHD. 

            The pulmonary component may be thought of in terms of decreasing or increasing resistance to blood flow across the pulmonary vascular bed.  Patients need a low pulmonary vascular resistance, as well as unobstructed pulmonary arteries.  Normal lung parenchyma with no pulmonary vascular disease is typically a low resistance system (e.g. 1 Woods unit). Events that may raise PVR such as acidosis, hypercarbia and hypoxia will be harmful.  Ventilator settings should include low (<15-20 mm Hg) mean airway pressures and normal alveolar ventilation.   Overventilation with high airway pressures (e.g. Valsalva breaths) and the resultant decrease in venous return and increased PVR may be more harmful than hypoventilation, atelectasis and the resulting hypercarbia/acidosis.  High levels of PEEP will increase pulmonary vascular resistance and cause a decrease in pulmonary blood flow. 

            In terms of cardiac effects on Fontan physiology, the maintenance of NSR with normal systolic and diastolic function is important.  Ideally there will be no outflow obstruction and a competent valve system.

            In summary the most important objective when caring for patients with Fontan physiology include maintenance of adequate intravascular volume or preload.  An appropriate ventilation strategy which minimizes high mean airway pressures, while also preventing atelectasis, hypoxia and hypercarbia is important.  Cardiac function should be maintained as NSR with optimal performance.

Dr. Cripe has recently completed his training in Anesthesiology at the University of Pennsylvania

The Frank Murphy Memorial Lecture 2008 - Congenital Heart Diseases

Chad Cripe, M.D., gave the Frank Murphy Memorial Lecture for 2008 on the subject of the implications of congenital heart disease in adults (CHD).  His major points for CHD are as follows:

Congenital heart diseases (CHD) may encompass a number of different structural lesions in the fetal circulation that persist after birth.  Some may be life threatening, requiring immediate surgical correction.  Others may go unnoticed until symptoms of advanced disease present themselves.  A physiologic classification of CHD exists in order to allow grouping of similar lesions.  These classifications include shunts, mixing lesions, obstructive lesions and regurgitant lesions. 

Shunts are lesions that produce abnormal blood flow within the heart from left to right or right to left.  In left to right shunts, such as ASD, VSD and PDA, some of the blood in the left side of the heart is directed to the right side of the heart without being delivered to the peripheral circulation.  This creates an excess volume overload on the heart.  In the case of right to left shunts, such as in Tetralogy of Fallot, Pulmonary Atresia and Eisenmenger complex, blood is diverted to the left heart without picking up much needed oxygen in the lungs.  This creates problems of hypoxia for these patients. 

Mixing lesions, such as transposition of the great arteries, tricuspid atresia and univentricular heart, represent the most complex type of CHD.  As the term mixing lesion implies, there is often a mixing of oxygenated and deoxygenated blood occurring in these patients.  The degree of mixing is often represented by the Qp:Qs ratio.  Qp represents flow to the pulmonary system, whereas Qs represents flow to the systemic circulation.  In healthy individuals the Qp:Qs ratio is approximately 1:1 (there exists a small amount of blood that is diverted back to the right heart from the pulmonary/bronchial circulation and cardiac thesbian vessels without being oxygenated).  The degree of shunting is variable and may often change quickly depending on the patient’s clinical situation.  Factors that increase or decrease pulmonary vascular resistance (PVR) will directly affect the Qp:Qs ratio.  Patients often develop some degree of cyanosis.  Changes in vascular resistance can also affect patients with shunting lesions.  For example, in patients with Tetralogy of Fallot, an increase in systemic vascular resistance leads to increased pulmonary blood flow and improved oxygenation.  In contrast, systemic vasodilation often leads to increased right to left shunt, hypoxia and cyanosis.

Obstructive lesions include pulmonic stenosis, aortic stenosis, coarctation of the aorta, mitral stenosis and hypoplastic left heart syndrome.  In these situations the heart sees a pressure overload as a result of the obstruction.  Signs of pressure overload may develop such as an increase in systolic and diastolic BP and and an increase in LV wall thickness. 

Regurgitant lesions are rare in CHD, yet may be seen commonly in some adult settings.  Ebstein’s anomaly is a congenital downward displacement of the tricuspid valve which occurs rarely in newborns.  The tricuspid valve becomes regurgitant and signs of volume overload may occur, such as an increase in diastolic BP, wall thickness and radius of the ventricle.

Dr. Cripe has recently completed his training in Anesthesiology at the University of Pennsylvania

When to give muscle relaxants after anesthesia induction

A recent editorial and a letter to the editors of Anaesthesia challenge the usefulness, safety and validity of the teaching that one should “prove the ability to ventilate by mask before giving a muscle relaxant”.  Both authors claim that the opposite may occur; that the act of trying to ventilate a lightly anesthetized patient by mask may actually create the airway obstruction and that NMBs are probably a better rescue approach for not being able to ventilate than hoping the patient will resume spontaneous ventilation. Refs: Calder I: Could “safe practice” be compromising safe practice? Should anaesthetists have to demonstrate that face mask ventilation is possible before giving a neuromuscular blocker? Anaesthesia 2008;63:113-115; Priebe HJ: Could “safe practice” be compromising safe practice? Should anaesthetists have to demonstrate that face mask ventilation is possible before giving a neuromuscular blocker (letter)? Anaesthesia 2008;63:671-672.

Dr. Levy a senior faculty member at the University of Pennsylvania rebuts as follows: “the assumption by both the editorial and the letter to the editor  is that the inability to ventilate the patient will not result in a change in clinical approach and that, in most cases, the administration of a neuromuscular blocking drug will occur anyway. What the authors failed to consider is that, based on the ability (or inability) to ventilate, the selected neuromuscular blocking drug may change. For example, instead of giving vecuronium, one might opt to use succinylcholine for more rapid onset. Even if face mask ventilation were successful, one might elect a more rapidly acting agent if there were considerable difficulty in obtaining air exchange. Although this does not invalidate the arguments presented, it does suggest that more complete consideration of the process might lead to different conclusions than those presented.”

Warren Levy, M.D., is Associate Professor of Anesthesiology and Critical Care at the University of Pennsylvania

David S. Smith, M.D., Ph.D.

Nasotracheal and orotracheal intubation are both associated with a about a 12% incidence of bacteremia but this may not be clinically significant

Valdes et al did a prospective study of 110 patients undergoing surgery under general anesthesia.  Venous blood samples were obtained before and then 30 seconds after intubation.  Bacteremia after tracheal intubation was detected in 6 of 50 patients who had orotracheal intubation and 7 of 60 patients after nasotracheal intubation.  Seven of the isolates (54%) were resistant to oxicillin.  Two patients had positive pre intubation blood cultures.  The authors discuss the controversy concerning the need of antibiotic prophylaxis for tracheal intubation in patients at risk for bacterial endocarditis.  They suggest that antibiotic prophylaxis should be considered after both orotracheal and nasotracheal intubation.  Valdes C et al: The incidence of bacteraemia associated with tracheal intubation.  Anaesthesia 2008;63:588-592.

PJ Brennan, an infectious disease specialist at the University of Pennsylvania raises concerns about the potential conclusions of this article. “I just want to note that bacteremia after events involving disturbance of colonized mucosal surfaces results in transient bacteremia very frequently. Dental procedures are best known for such events but many other procedures including tooth brushing, endoscopy, bowel movements and child birth are all associated with the common occurrence of bacteremia – most of these are reported to be more common than the incidence reported here after intubation. I suspect that any interruption of a mucosal surface, however minor, can cause bacteremia. The key issue is the incidence of endovascular infection after such events. In all other settings bacteremia is transient and the establishment of an endovascular infection is rare. The factors in determining prophylaxis include not only the bacteremia, which is a given, but the cardiovascular risk as well. I would not want to see this become a practice we adopt given the frequency of the index event (intubation), the infrequent nature of the adverse event (endovascular infection), the tenuous cause and effect association and the hazard of antibiotics and drug resistance.”

PJ Brennan M.D. is Professor of Medicine, Division of Infectious Diseases and Chief Medical Officer for UPHS.

David S. Smith, M.D., Ph.D.

Bad news for tight intraoperative glucose control

Dr. Kofke calls our attention to this prospective randomized study of tight intraoperative glucose control using insulin infusion compared to “conventional” management with tight control in both groups during the post operative period.  Four hundred cardiac surgery patients were randomly assigned to tight glycemic control (blood glucose levels between 80 – 100 mg/dl) during surgery or conventional glucose control.    Patients who did not become hyperglycemic during surgery were not included in the analysis.  Pre operatively the glucose levels were similar in both groups.  At the conclusion of cardiopulmonary bypass the mean blood glucose level in the tight control group was significantly lower (123 mg/dl) compared to 148 mg/dl in the conventional glucose control group.  All patients in the intensive treatment group received insulin during surgery and 15% of the patients in the conventional therapy group received insulin.  At the end of 24 hours in the ICU the mean glucose levels were the same in both groups (about 106 mg/dl, mean).  The two groups did not differ in the primary composite endpoint of sternal infection, death, prolonged ventilation, cardiac arrhythmias, stroke or renal failure.  Nor did investigators find a direct benefit from intraoperative from intensive insulin therapy for and of the individual components of the composite end point.  In fact the reverse result was obtained.  The intensive treatment group had significantly more strokes (8 vs. 1) and deaths (4 vs. 0) than the conventional treatment group.  There was no treatment effect for length of stay in the ICU or hospital.  The authors note that this does not directly contradict prior findings of benefits from tight glucose control as the key studies involved tight control vs. conventional control during the entire period from OR through ICU.  It is possible that tight glucose control during the relatively brief period of surgery is not as important as tight glucose control during the longer post operative period.  Gandhi GY et al: Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery.  Ann Intern Med 2007;146:233-243

Dr. WA Kofke is Professor of Anesthesiology at UPENN

David Smith, M.D., Ph.D.

Lots of pain in the United States

Krueger and Stone used a telephonic random digit dialing technique in an attempt to contact 10700 people to seek their participation in a survey about the occurrence and severity of pain across randomly sampled 15 minute intervals of the day. Their final sample was 3982 people (a 37% response rate).  They used a 7 choice rating scale for pain intensity and found that 28% of men and 26% of women reported feeling some pain at the sampled times.  Those with lower income or less education spent a higher proportion of their time in pain and reported a higher proportion of time in pain than did those with higher income and more education.  The authors note the high cost of pain with respect to medication and lost time from work.  They estimate that the combined cost of outpatient prescription analgesics and lost productivity was nearly 75 billion dollars.  Krueger AB and Stone AA: Assessment of pain: a community-based diary survey in the USA.  Lancet 2008;371:1519 - 1525

David S. Smith, M.D., Ph.D.

Edema after lung resection? Try aerosolized salbutamol

Patients after lung resection have a 2-5% incidence of acute lung edema even when precautions such as low tidal volumes, PEEP, recruitment maneuvers and fluid restriction are used.  The authors built on existing information about the role of epithelial B-adrenergic receptors in the regulation of active sodium transport mediated clearance of excess intra-alveolar fluids and prior studies showing that B-adrenergic agonists attenuate lung vascular injury and accelerate the resolution of alveolar edema to design a cross-over study to examine the effects of a B-adrenergic agonist (salbutamol) on lung water after lung resection.  They enrolled 21 patients they determined to be at high risk for postoperative lung edema.  All patients had thoracic epidural anesthesia, double lumen tubes and were extubated at the completion of surgery.   Post operatively the patients were administered either 5 mg of nebulized salbutamol or ipratropium (an anticholinergic bronchodilator) in a cross over design with a 6 hour washout period between drugs.  Preoperatively this high risk group had a mildly elevated extravascular lung water index (EVLWI) of 7 – 8 ml/kg.  Post-operatively, but before the study drug, the EVLWI was increased above the preoperative value to 10 and the ratio of PaO2/FiO2 was decreased.  On post operative day 0, salbutamol nebulization induced a reduction of EVLWI and increased the PaO2/FiO2 ratio.  In contrast nebulized ipratropium produced no changes in these variables.  Salbutamol also increased cardiac contractility and cardiac index.  Thus nebulized salbutamol reduced pulmonary water content, enhanced cardiac performance and improved oxygenation in this group of patients.  The study was too small to determine the impact of treatment on outcome.  Lecker M et al: Aerosolized salbutamol accelerates the resolution of pulmonary edema after lung resection.  Chest 2008;133:845-852.  There is an accompanying editorial on page 833 of the same issue.

David S. Smith, M.D., Ph.D.

An argument for NOT stopping antiplatelet drugs prior to surgery

The Anesthesia Pain Service Guidelines presented earlier call for stopping clopidogrel seven days prior to surgery if neuraxial anesthesia is desired.  It is important to note, however, there have been a number of reported cases of coronary artery occlusion in patients with drug eluting stents after temporary cessation of either aspirin or clopidogrel.  Bengeri (1) and Bolsin et al (2) argue that the risks of cessation outweigh the risk of increased surgical bleeding and that these antiplatelet drugs should be continued into the perioperative period.  Bolsin notes that they surveyed 24 patients with drug eluting stents who presented for a total of 43 non-cardiac surgery procedures.  On 15 occasions clopidogrel was stopped though aspirin was continued.  Three patients experienced myocardial infarction secondary to in-stent thrombosis.  Two of the three infarcts occurred prior to surgery.  Only one patient of the 24 experienced excessive bleeding.

            The American College of Cardiology/American Heart Association joint guidelines for reducing the risk of a perioperative cardiac event (3) emphasized the need to continue anti-platelet drugs perioperatively.  The cases presented by Bengeri and by Bolsin et al together with the recommendations found in the ACC/AHA guidelines force the conclusion that antiplatelet drugs should not be discontinued prior to surgery in patients receiving these drugs after coronary stenting.  The Anesthesia Pain Service notes that epidural analgesia can be safely provided to patients taking aspirin.  In patients on clopidogrel, the drug should be continued preoperatively but epidural analgesia should not be offered.

1)      Bengeri S: Successful management of patients with a drug-eluting coronary stent presenting for elective surgery (letter).  BJA 2007;98:841-8

2)      Bolsin S et al: Comment on Bengeri 2007 (letter): BJA 2007;98:842

3)      Fleisher LA et al: ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for non cardiac surgery. http://circ.ahajournals.org

David S. Smith, M.D., Ph.D.

Package insert warnings for anti platelet or anticoagulant drugs

The package insert for Lovenox brand enoxaparin contains a black box warning about the association of this drug and hematomas after spinal or epidural anesthesia.  They note that the risk is increased by the presence of indwelling epidural catheters for analgesia, the presence of additional drugs that affect hemostasis such as NSAIDS or platelet inhibitors, and traumatic or repeated spinal or epidural puncture.  The package insert for Plavix brand clopidogrel contains no specific warnings about the concomitant use of this drug and regional anesthesia however it does warn that if a patient is to undergo elective surgery and an antiplatelet effect is not desired than clopidogrel should be discontinued five days prior to the procedure.

David S. Smith, M.D., Ph.D.

Orthopedic surgery, DVT prophylaxis and regional anesthesia

Orthopedic surgery is associated with a high incidence of thromboembolism and orthopedic surgeons have been among the most aggressive with respect to DVT prophylaxis.  Traditionally anesthesiologists have viewed many orthopedic surgery procedures as “perfect” for regional techniques such as spinal or epidural anesthesia.  Rowlingson et al is optimistic about the continued use of regional anesthesia in orthopedic patients who are receiving LMWH.  They note that “the key to optimizing patient safety however, depends on a careful calibration of the total daily dose and the timing of the first and subsequent doses of LMWH with the timing and management of the regional anesthetic procedure.”  I am not convinced that this degree of coordination and cooperation is possible particularly given the consequences (paralysis).  Dr. Richman at Penn Presbyterian Medical Center notes that most of their orthopedic surgeons use LMWH for post operative DVT prophylaxis and that patients receiving LMWH never get epidural anesthesia.  For knee surgery the anesthesiologists are using femoral nerve catheters sometime in combination with PCA.  They are willing to do spinal anesthesia as long the LMWH is not started until after surgery.  He notes that most of their orthopedic surgery patients receive general anesthesia (personal communication).

            

REF: Rowlingson JC, Hanson PB: Neuraxial anesthesia and low-molecular-weight heparin prophylaxis in major orthopedic surgery in the wake of the latest American Society of Regional Anesthesia Guidelines.  Anesth Analg 2005;100:1482-8

David S. Smith, M.D., Ph.D.