Medical Complications Related to Surgery
Sub-Sections:
1.
Cardiovascular Risk
2.
Pulmonary Disease
3.
Liver Disease and Bleeding Disorders
(Page 4)
(Page 8)
(Page 11)
This report was informed by discussions and consensus reached at the April 11-12, 2013 Workshop on the Harmonization of Living Donor Assessment and Acceptance Criteria. Due to time restraints at the
Workshop the sub-sections were further reviewed by Workshop attendees and by the Living Donation
Advisory Committee on May 31, 2013.
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Medical Complications Related to Surgery
Goals:
1.
Ensure safety of the surgical procedure for the donor.
2.
Detect unrecognized disease and potential medical risk factors and hence reduce peri- and postoperative medical complications related to the surgery
Background:
Overt disease will exclude most individuals as potential donors as only healthy individuals will pass the work-up process and be considered eligible as a living kidney donor. At this time consideration is directed toward the assessment of donor peri-operative risk. Living donors do not require surgery and have no clinical benefit from the donation and while surgery is part of an altruistic act it is never the less associated with morbidity and mortality. As such, potential living donors should undergo a more rigorous evaluation and stricter than usual criteria needs to be applied to define risk.
While the incidence of peri-operative complications is low, pulmonary embolus, bleeding and cardiac events have been reported. The issue is to identify the most appropriate method of determining which donors require additional testing to detect occult disease.
The overall surgical risk of donating a kidney is low in healthy individuals. The following gives a general overview about medical risk factors and complications related to the surgical procedure. The perioperative mortality is approximately 1 in 3,000 (0.03%) after open living donor nephrectomy (Bia MJ,
Transplantation 1995; 60: 322-7; Najarian JS, Lancet 1992; 340: 807-10; Bay WH, Ann Intern Med 1987;
106: 719-27; Kasiske BL, J Am Soc Nephrol 1996; 7: 2288-313). A recent study in more than 80,000 donors showed a 90 day mortality of 3.1 in 10,000 donations (0.01%), despite increasing age and obesity in the donor population (Segev DL, JAMA 2010; 303: 959-66). The most common causes of death after living donation are pulmonary emboli and cardiac events (myocardial infarction and arrhythmias)
(Najarian JS, Lancet 1992; Bennett AH, Surg Gynecol Obstet 1974; 139: 894-8; Uehling DT, J Urol 1974;
111: 745-6).
The peri-operative morbidity for living donor nephrectomy have been summarised for a large number of single centre studies (from UK guidelines; Kasiske BL, J Am Soc Nephrol 1996; 7: 2288-313). The mean overall complication rate was 32% and the major peri-operative complication rate was 4.4%. The estimated „major complication‟ rate in a survey by Bay and Hebert (Bay WH, Ann Intern Med 1987; 106:
719-27) was 1.8%, whereas the ASTP survey (Bia MJ, Transplantation 1995; 60: 322-7) reported that 22 out of 9,692 (0.23%) kidney donors experienced „potentially life-threatening or permanently debilitating‟ complications. An overview of peri-operative complications is given by Kok NF et al (Kok NF,
BMJ 2006; 333: 221). Specific surgical complications after living donation include wound related problems such as sepsis, hernia and chronic pain, conversion from laparoscopic to open surgery, bleeding, requirement for blood products and cosmetic consequences.
Potential medical risk factors associated with peri-operative complications in patients requiring general surgery are:
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Medical Complications Related to Surgery

Exercise Capacity – key determinant of overall surgical risk. The ability to walk two blocks on level ground or carry two bags of groceries up one flight of stairs without symptoms can give a rough assessment. These activities expend approximately 4 metabolic energy equivalents
(METS) and translate into a low risk for major postoperative complications.
A functional capacity of > 4 METS predicts a very low peri-operative risk (Reilly DF, Arch Intern

Med 1999; 159: 2185–92; Older P, Chest 1999; 116: 355-62).
Age – independent risk factor for post-operative pulmonary complications but predominantly due to increasing numbers of co-morbidities associated with aging. A comparison of older and younger donors regarding operative time, surgical blood loss and length of hospital stay did not show significant differences (Smetana GW, Ann Intern Med 2006; 144: 581). A meta-analysis indicated that surgical complications were not significantly higher for older or obese donors
(Young A, AJT 2008; 8: 1878).

Obesity – is not a risk factor for most major adverse postoperative outcomes, with the exception of pulmonary embolism. Obesity increases the rates for wound infections (Dindo D,
Lancet 2003; 361: 2032; Herrera FA, Am Surg 2007; 73: 1009; Hofer RE, Mayo Clin Proc 2008; 83:
908; Smetana GW, NEJM 1999; 340: 937), for deep venous thrombosis and associated pulmonary embolism (Smetana GW, Ann Intern Med 2006; 144: 581). Obese and non-obese
(usu. < 30 kg/m 2 ) donors were compared on operative time, blood loss and hospital stay.
Differences were statistically significant but clinically insignificant. Surgical complications (e.g. minor infections, hemorrhage, pneumonia or pneumothorax) were not significantly higher for older or obese donors (Young A, AJT 2008; 8: 1878).

Obstructive Sleep Apnea – increases the risk for postoperative medical complications including hypoxemia, respiratory failure, unplanned re-intubation, and ICU transfer (Kaw R, Chest 2012;
141: 436). As most patients are undiagnosed it is reasonable to screen patients for obstructive sleep apnea before surgery.

Alcohol misuse – patients who misuse alcohol on a regular basis have an increased risk for postoperative complications including surgical site infections, other infections and cardiopulmonary complications (Harris AH, J Bone Joint Surg Am 2011; 93: 321).

Smoking – current smoking is associated with postoperative morbidity and mortality, smoking cessation leads to decreased wound healing complications and pulmonary complications (Jones
R, Interact Cardiovasc Thorac Surg 2011; 12: 449; Mills E, Am J Med 2011; 124: 144; Myers K,
Arch Inter Med 2011; 171: 983).

Anaesthetic Complications – malignant hypertension is a rare, inherited complication. The preoperative assessment should include questioning about either personal or family history of complications from anaesthesia.
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Medical Complications Related to Surgery
All living donor candidates should undergo minimal testing and assessment according to current
American Heart Association ( www.heart.org
) and the Canadian Heart and Stroke Foundation
( www.heartandstroke.com
) guidelines.
Gender:
 Men over the age of 55 and postmenopausal women are at greater risk of heart disease. Until women reach menopause they have a lower risk of stroke than men.
Family History:
 The risk of heart disease is increased if close family members (parents, siblings or children),
 developed heart disease before age 55 or, in the case of female relatives, before menopause.
The risk of stroke is increased if close family members – parents, siblings or children – had a stroke before age 65.
Ethnicity:
 First Nations people and those of African or South Asian descent are more likely to have high blood pressure and diabetes, and therefore are at greater risk of heart disease and stroke than the general population.
Communication with the living donor candidate and if necessary the candidate’s family doctor over the timeframe following initial acceptance as a living donor candidate, is essential for ensuring the potential donor continues to be considered as a suitable candidate. Cardiovascular risk is one area that may need ongoing or further investigation pending the time lapse since registration.
1.
Additional testing is indicated in the following potential donors as per current American
Heart Association/Canadian Heart and Stroke Foundation Guidelines: i.
Men 50 and older* ii.
Women 60 and older* iii.
Where calculated 10-year cardiovascular disease risk of >10% based on Framingham risk calculator or other similar calculator* iv.
Potential donors with one or more cardiovascular risk factors (hypertension, hypercholesterolemia and smoking)*
*according to cardiovascular risk calculator and documented
2.
If there is a change in risk factors since initial assessment a cardiology consultation is appropriate.
1.
Based on total assessment findings and in accordance with current American Heart
Association/Canadian Heart & Stroke Foundation guidelines
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Medical Complications Related to Surgery
1.
To be considered in conjunction with the medical questionnaire, the physical examination, functional capacity, ECG & Chest X-ray and cardiology report.
References
A.
Background Information Summarizing the Literature:
The major predictors of surgical complications related to cardiovascular disease are:

High-risk surgery (vascular, cardiovascular)

History of ischemic heart disease

History of congestive heart failure

History of cerebro-vascular disease

Diabetes treated with insulin

Significantly reduced GFR
None of these will apply to appropriately selected living kidney donors. Nephrectomy is not considered a high risk operation; people with known cardiovascular disease, diabetes or significantly impaired kidney function are excluded from donating according to international guidelines and Canadian practice.
The ACC/AHA guidelines which apply to individuals undergoing non-cardiac surgery do NOT recommend any further cardiac testing for those with no active heart disease who have reasonable functional capacity (defined as

4 METS). These guidelines do NOT recommend baseline ECG for individuals with no risk factor for cardiac disease.
However, as explicitly described in the UK guidelines, the transplant community has established that living donors should undergo more rigorous evaluation given that donation is an altruistic act associated with morbidity and potentially mortality.
B.
Literature
The issue is: “What is the most appropriate method of determining which donors require additional CV testing to detect occult coronary artery disease?”
The literature suggests two approaches. a.
One is to use conventional risk factors and available calculators to determine whether an individual is at low (<10%), intermediate (10-20%) or high risk (>20%) for a cardiovascular event in the next 10 years, and perform further testing on those above a certain risk level, usually >10%. To put this in perspective, for non-smoking men with systolic BP of 130 and total cholesterol/HDL cholesterol ratio of 4, the 10year risk of CVD increases with age and reaches a value of >10% around age 55; for women with similar characteristics, a risk of >10% is not reached until age 65-70
(see attached graph). b.
The second is to assess the donor’s functional capacity by determining his ability to perform various tasks which can be converted into METS. Impaired functional capacity (<4 METS) has been associated with increased peri-operative risk. Good exercise tolerance is an excellent predictor of good outcomes, even when coronary
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Medical Complications Related to Surgery disease exists. The ACC/AHA Guidelines identify poor functional capacity (<4 METS) as a potential indication for further cardiac testing, but only if there are other cardiac risk factors or high risk surgery.
C.
Summary of UNOS cardiovascular guidelines a.
Chest X-ray b.
ECG c.
ECHO and/or exercise stress test if the prospective donor is over 50 years old or has a risk factor (hypertension, smoking, hyperlipidemia, family history, shortness of breath from exercise) or physical findings that demonstrate increased risk for heart disease including, but not limited to, borderline blood pressure, abnormal ECG, abnormal CXR, murmur d.
Pulmonary function tests for smokers
D.
Summary of UK cardiovascular guidelines a.
A low threshold should be set for screening potential donors for cardiovascular disease, and for their exclusion from donation b.
Potential donors with an exercise capacity of < 4 METS or >10% estimated risk of significant coronary atherosclerosis should undergo formal cardiological assessment c.
Potential donors with exercise capacity >10 METS are at very low cardiac risk d.
Screening of higher risk donors should be performed by CT calcium scoring and/or functional assessments such as dynamic stress tests.
E.
Canadian Practice:
All request ECG. No uniform practice with respect to stress testing or echocardiography (see the table on Current Canadian Practice for Testing in references under Anaesthetic Reactions).
F.
References:
These recommendations for testing for cardiovascular disease in potential living kidney donors derive from the following sources: a.
UNOS guidelines (2007) b.
UK guidelines (2011) c.
Guidelines for peri-operative cardiovascular evaluation and care for non-cardiac surgery: American College of Cardiology/American Heart Association (2007) d.
Current Canadian practice, derived from the survey of Canadian kidney transplant programs (2012)
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Medical Complications Related to Surgery
University of Edinburgh Risk Calculator
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Medical Complications Related to Surgery
While some pulmonary conditions would not necessary negate kidney donation, they regardless pose significant peri-operative risk to the donor candidate. These conditions include a history of asthma, smoking, sleep apnea and chronic obstructive lung disease.
1.
Additional testing is indicated as applicable in the following situations: i.
Age > 50 yrs (suggest 1.) ii.
Smoking history (suggest 1.) iii.
Chronic obstructive lung disease iv.
Asthma v.
Obstructive sleep apnea vi.
Unexplained dyspnea and/or cough
2.
Regarding the diseases iii - vi in conjunction with an anaesthesia and/or pulmonary consult additional testing (see below tests i- v) should be undertaken to estimate disease severity and associated medical risk : i.
Pulmonary risk indices calculations (Arozullah AMl, Ann Surg 2000; 232: 242; Canet
J, Anesthesiology 2010; 113: 1338) ii.
Pre-operative oxygen saturation iii.
Pulmonary function testing iv.
Exercise testing (see also cardiovascular stress testing) v.
Arterial blood gases
1.
Negative history and physical exam – no concerns
2.
Age > 50 yrs. – no concerns (but information regarding risk of post-operative pulmonary complications should be given based on risk indices calculations) (Smetana GW et al, Ann Intern
Med 2006; 144: 581; Arozullah AM, Ann Surg 2000; 232: 242; Canet J, Anesthesiology 2010; 113:
1338).
3.
Smoking history – no concerns if overall assessment and determination shows minimal risk and no sign of compromised pulmonary function (see also risk cardio-renal disease)
4.
Asthma – depending on additional tests and Anaesthesia & pulmonologist consult
1.
Exercise capacity < 4 METS (Fleisher LA, Circulation 2009; 120: e169; Hlatky, Am J Cardiol 1989;
64: 651)
2.
Chronic lung disease with impairment of oxygenation or ventilation
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Medical Complications Related to Surgery
3.
Obstructive sleep apnea – mild sleep apnea might be accepted but only in conjunction with an anaesthesia and/or pulmonary consult, obstructive sleep apnea associated with pulmonary hypertension will be excluded.
References
A.
Background Information Summarizing the Literature: a.
Postoperative pulmonary complications add significantly to morbidity and mortality b.
Major risk factors for postoperative pulmonary complications such as chronic lung disease, poor general health status, pulmonary hypertension, heart failure, metabolic factors are unlikely to occur in living donors after they have passed the work-up process c.
Simple screening questionnaires and a thorough physical examination will rule out, to a large extent, significant pulmonary diseases d.
contributing clinical findings are more predictive of the risk of postoperative pulmonary complications than are spirometric results (Lawrence VA, Chest 1996;
110: 744)
B.
Literature: a.
In the guidelines from the different national committees, pulmonary risk evaluation is included in the cardiovascular risk assessment (see below the table summarizing the UK, UNOS and Australian guidelines). The Current Canadian Practice for Testing is shown below as a table. b.
Electronic textbook ‘UpToDate.com – website www.uptodate.com 2013’; gives an excellent overview about risk and medical complications with general surgery. This information is not covered sufficiently by the existing living donor literature and the international guidelines. As such two topics for this workbook were chosen from
UpToDate:

Smetana GW. Preoperative medical evaluation of the healthy patient. Last updated Nov 2, 2012

Smetana GW. Evaluation of preoperative pulmonary risk. Last updated Jan 24,
2013 c.
Selected articles:

Arozullah AM, Ann Surg 2000: 232: 242.

Brooks-Brunn JA. Chest 1997; 111: 564.

Canet J et al, Anesthesiology 2010; 113: 1338.

Chung F et al, Anesthesiology 2008; 108: 812.

Fleisher LA, et al, Circulation 2009; 120: e169.

Hlatky et al, Am J Cardiol 1989; 64: 651.

Kaw, et al, Chest 2012; 141: 436.

Kroenke K et al, Chest 1993; 104: 1445.
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Medical Complications Related to Surgery

Lawrence VA, et al, Chest 1996; 110: 744.

Lawrence VA et al, Arch Intern Med 1989; 149: 280.

McAlister FA et al, Am J Respir Crit Care Med 2003; 167: 741.

Nakagawa M et al, Chest 2001; 120: 705.

Qaseem A et al, Ann Intern Med 2006; 144: 575.

Smetana GW et al, Ann Intern Med 2006; 144: 581.

Smetana GW et al, NEJM 1999; 340: 937.
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Medical Complications Related to Surgery
Hematological abnormalities and diseases can place both the donor and recipient at risk. A history of prior jaundice; alcohol intake; liver disease; bleeding disorders including anaemia and bruising; and clotting disorders (deep venous thrombosis or pulmonary embolism) should be obtained at the time of the medical history and physical examination.
1.
Hematology and hepatology consultations may be indicated for investigation of a history of bleeding or thrombosis, or abnormalities in liver function tests uncovered during screening investigations.
1.
Acceptance in consideration of overall clinical assessment and peri-operative risk
1.
To be determined following full clinical evaluation
References
A.
Background Information Summarizing the Literature: a) Rationale
The presence of an underlying bleeding or clotting disorder places a living donor at a higher risk of significant bleeding complications or thrombotic complications.
As such, potential living donors should be evaluated for such disorders prior to surgery b) Background
European Best Renal Practice Guidelines (EBPG) – no comment
UK Guidelines (2011) – Assess for history of thromboembolic disease. Measure PT/PTT, CBC; thrombophilia screen where indicated.
UNOS – Assess for history of clotting disorders or DVT.
Canadian Practice- a scan shown below in the table – PT/PTT in almost all centres. Platelet count in the minority (per survey, but in practice, universally available with CBC).
In 1983, Rapaport published a seminal review of pre-operative hemostatic evaluation, and his recommendations remain relevant. He recommended that patients who undergo surgery should be questioned about their response to various bleeding challenges, and recommended seven
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Medical Complications Related to Surgery questions, which have been expanded below:
1.
Do you experience excess bleeding in your mouth or frequent nosebleeds?
2.
Have you bled into a muscle or a joint?
3.
Have you ever had blood in your stool?
4.
Do you have profuse menstrual bleeding?
5.
Do you develop large bruises even in the absence of obvious injury? Have you bled excessively after small wounds?
6.
Have you had teeth extracted? How long did you bleed? Was the bleeding immediate or delayed?
7.
What operations have you undergone, including minor procedures such as skin biopsies or colonoscopy/bronchoscopy with biopsies? Was there any bleeding, either immediate or delayed?
8.
Do you have other medical problems? Is there a history of hepatic, renal, or hematologic disease? Have you ever required a transfusion of whole blood, red blood cells, platelets, plasma, or blood clotting factors?
9.
What medications are you taking? Do you take anticoagulant medications? Have you taken aspirin or other pain relievers within the last 10 days? Do you take over-thecounter remedies, supplements, or alternative medicine (e.g., herbal preparations)?
10.
Do any relatives have bleeding tendencies or experience excessive bleeding following surgery?
A positive history should prompt further evaluation, and referral to a hematologist, if indicated.
However, the history may be unreliable. This can be due to a poor history (i.e., the forgetful physician), an unreliable patient (forgetful or unaware), an unchallenged patient (no prior surgeries/extractions), or an acquired disorder. For these reasons, basic screening in the form of a PT/PTT and platelet count is recommended for moderate or high risk surgery.
B.
Literature:
Guidelines for the Medical Evaluation of Living Kidney Donors (Living Donor Committee). OPTN,
U.S Department of Health & Human Service. Visited on March 11, 2013. http://optn.transplant.hrsa.gov/PublicComment/pubcommentPropSub_208.pdf
European Renal Best Practice (ERBP) Guideline on kidney donor and recipient evaluation and peri-operative care, Draft 7. Visited on March 7, 2013. http://www.european-renal-best practice.org/sites/default/files/u33/ATT00349.pdf
United Kingdom Guidelines for Living Donor Kidney Transplantation, third edition, May 2011. www.bts.org.uk & www.renal.org
Rapaport S. Pre-operative hemostatic evaluation: which tests, if any? Blood, 1983; 61: 229-231
Coutre S. Preoperative assessment of hemostasis. In: UpToDate, Leung LLK (Ed), UpToDate,
Waltham, MA, 2013
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Medical Complications Related to Surgery
D. International Assessment and Acceptance Criteria Living Kidney Donation (selected in relation to all topics in this work group)
Assessment UK US AUS ERBP
2013
Cardiovascular
Surgery: Donor
Risk and Peri-
Operative Care
2011 2008 2007-2010
- low threshold for screening for CV disease and exclusion from donation (B1)
- potential donors with an exercise capacity of
<4 METS or >10% estimated risk of significant coronary atherosclerosis should undergo formal cardiological assessment (B1)
- potential donors with exercise capacity >10
METS are at very low cardiac risk (B1)
- screening of higher risk donors should be performed by CT calcium scoring and/or functional assessments such as dynamic stress tests (B2)
- all LDs should receive adequate thromboprophylaxis. Intraoperative mechanical compression and postoperative compression stockings, along with
LMW heparin, are recommended (A2)
- pre-operative hydration with an overnight infusion and/or fluid bolus
- ECG
- ECHO and/or exercise stress test if
> 50 yrs or risk factors (HTN, smoking, lipids, FH, dyspnea on exercise) or physical findings indicating increased risk for heart disease incl. borderline blood pressure, abnormal
ECG, abnormal CXR, murmur
- pulmonary function tests for smokers
Based on level III &
IV evidence
- in open surgery, the risks appear related to perioperative complications incl. pulmonary emboli, pneumonia and ischemic events
- with laparoscopic surgery,
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Medical Complications Related to Surgery
Assessment UK
2011
US
2008
AUS
2007-2010
Contraindications during surgery may be beneficial for laparoscopic donor nephrectomy (B2)
- Laparoscopic donor surgery is the preferred technique for LD Nx, offering a quicker recovery, shorter hospital stay and less pain. Mini-incision surgery is preferable to standard open surgery
(B1) complications are largely due to catastrophic intraoperative events related to securing of the vascular pedicle. Measures to reduce these specific problems should be undertaken and tailored to the technique used by individual transplant units
- death and major complications occur infrequently following donor Nx.
This limits the feasibility of randomized controlled trials comparing donor surgical techniques.
The best available evidence over time with comprehensive registry data.
- history of thrombosis or embolism
- obesity: BMI >35
- coronary artery disease
- symptomatic valvular disease
- chronic lung disease with impairment of oxygenation or
- coagulation screen
(PT and APTT)
ERBP
2013
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Medical Complications Related to Surgery
Assessment UK
2011
US
2008 ventilation
- peripheral vascular disease
Relative CI:
- moderate Cardiac
Valvular disease with otherwise normal
ECHO findings
- mild sleep apnea without pulmonary hypertension
AUS
2007-2010
ERBP
2013
TEST
EKG
MIBI
CXR
PTT
INR
Platelets
BMI
AST
ALK Phos
GGT
Bilirubin
LDH
OTHER
Y
Y
Y
Y
N
SPH VGH FMC UAH STP TM LHSC SJH
CENTRES
SMH TGH TOH MUHC CHUM-ND HMR CHUQ QEII
TOTAL/16
Testing
Done
Testing
Not Done
Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y 16 0
N N N Y* N N Y N Y N N Y N Y Y N
6
10
Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y
16
0
Y
Y
Y
Y
Y
Y
Y
N
N
Y
Y
Y
Y
Y
Y
Y
Y
Y
N
N
N
Y
Y
N
Y
Y
N
Y
Y
N
Y
Y
N
Y
Y
N
Y
Y
N
Y
Y
N
Y
Y
N
N
N
N
14
13
5
2
3
11
Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y
16
0
Y
Y
Y
Y
N
Y
Y
Y
Y
Y
Y
Y
N
Y
N
Y
N
Y
Y
N
Y
Y
Y
Y
Y
N
N
N
N
N
ECHO
Y
Y
Y
Y
N
Y
Y
N
Y
N
Y
N
N
Y
N
ECHO
SECHO
>40
Y
N
Y
Y
N
Y
N
Y
Y
N
Y
N
Y
Y
Y
Y
Y
N
Y
Y
Sress ECG
Cardiac US ECHO
Y
Y
Y
Y
N
Y
N
N
Y
N
15
9
10
15
4
1
7
6
1
12
Y
N
Legend
Testing Done
Testing Not Done
Additional Tests
Additional Comments*
UAH - MIBI - >60 y.
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