liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Diabetes and Coronary Surgery: Metabolic and clinical studies on diabetic patients after coronary surgery with special reference to cardiac metabolism and high-dose GIK
Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction An increasing proportion of the patients undergoing cardiac surgery have diabetes mellitus, in particular type II diabetes. In spite of this, diabetic patients have received limited attention in this setting. Although diabetes is a metabolic disease cardiac metabolism in association with surgery has previously not been explored in diabetics. This investigation was carried out to describe the metabolic state of the heart in diabetics after cardiac surgery and to study if it is accessible to metabolic intervention with high-dose GIK. Also, the potential hazards associated with such a regime in clinical practice were evaluated. Furthermore, a comparison of the outcome in diabetic and nondiabetic patients after coronary surgery was done.

Methods Myocardial metabolism and how it was influenced by high-dose GIK was assessed with coronary sinus catheter technique in a prospective randomized study on 20 type II diabetic patients undergoing CABG (paper I, II). Safety issues concerning high-dose GIK were assessed in two retrospective studies. The potential role of metabolic interventions for neurological injury was assessed in a cohort of 775 consecutive patients undergoing CABG or combined CABG + valve surgery, in whom metabolic interventions gradually replaced traditional treatment for postoperative heart failure (paper III). A detailed analysis of blood glucose and electrolyte control was done in all cases (n=89) receiving high-dose GIK during one year (paper IV). The hemodynamic impact of highdose GIK was assessed with standard postoperative monitoring including Swan-Ganz catheters (paper II, IV). Outcome and prognosis after CABG in diabetic patients (n=540) were compared with nondiabetics (n=2239) with the aid of the institutional database comprising all isolated CABG procedures from 1995-1999 (paper V).

Results The metabolism of the diabetic heart after CABG was characterized by predominant uptake of FFA and restricted uptake of carbohydrate substrates. A high extraction rate of beta-hydroxybutyric acid and glutamate was also found. Alanine was released from the heart (paper I). High-dose GIK induced a shift towards uptake of carbohydrates, in particular lactate, at the expense of FFA and betahydroxybutyric acid (paper II). A substantial systemic glucose uptake was found during high-dose GIK treatment but the uptake tended to be lower and blood glucose higher if adrenergic drugs were used or/and if the patient was a diabetic (paper IV). High-dose GIK was associated with beneficial effects on cardiac output both in the prospective and retrospective analyses (paper II, IV). No evidence for untoward neurological effects associated with GIK treatment was found. History of cerebrovascular disease was the most important risk factor for postoperative cerebral complications and in general markers for advanced atherosclerotic disease were found to be of importance (paper III). High-dose GIK in clinical practice was associated with acceptable blood glucose and electrolyte control and no serious adverse events were recorded (paper IV). Patients with diabetes undergoing CABG had an acceptable short-term mortality that did not differ significantly from non-diabetic patients. However, diabetic patients had a higher early postoperative morbidity particularly with regard to stroke, renal- and infectious complications. Also, long-term survival was markedly reduced in diabetic patients, particularly in insulin treated patients (paper V).

Comments FFA were the main source of energy for the heart in type II diabetics after CABG whereas the uptake of carbohydrates was restricted. The high extraction rates of beta-hydroxybutyric acid and glutamate may represent an adaptation to the unfavorable metabolic situation of the post-ischemic diabetic heart. High-dose GIK can be used in type II diabetic patients after cardiac surgery to promote carbohydrate uptake at the expense of FFA and beta-hydroxybutyric acid. The magnitude of this shift was sufficient to account for the entire myocardial oxygen consumption assuming that the substrates extracted were oxidized. This could have implications for the treatment of the diabetic heart in association with surgery and ischemia. Provided careful monitoring high-dose GIK can be safely used in clinical practice and this treatment deserves further evaluation in the treatment of postoperative heart failure. High-dose GIK also provides a means for strict blood glucose control and as substantial amounts of glucose can be infused even in critically ill patients, it may prove useful for nutrition in critical care. Several of the risk factors for neurological injury identified constitute markers for advanced atherosclerotic disease, thus, also providing an explanation for the increased risk of neurological injury in diabetics after cardiac surgery. Short-term mortality was acceptable in diabetics after CABG. However, further efforts are warranted to address postoperative morbidity and late outcome. This represents a challenge as diabetic patients are accounting for an increasing proportion of the patients undergoing CABG.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2001. , 64 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 687
Keyword [en]
diabetes, heart, coronary surgery, cardiac surgery, myocardial metabolism, free fatty
National Category
Surgery
Identifiers
URN: urn:nbn:se:liu:diva-5219ISBN: 91-7219-982-2 (print)OAI: oai:DiVA.org:liu-5219DiVA: diva2:21174
Public defence
2001-09-28, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Note
On the day of the public defence the status of article IV was: Submitted and the title of article IV was in the printed version: High-dose GIK in cardiac surgery - clinical safety issues and lessons learned.Available from: 2001-10-11 Created: 2001-10-11 Last updated: 2012-01-24Bibliographically approved
List of papers
1. Myocardial uptake and release of substrates in type II diabetics undergoing coronary surgery
Open this publication in new window or tab >>Myocardial uptake and release of substrates in type II diabetics undergoing coronary surgery
2001 (English)In: Scandinavian cardiovascular journal : SCJ, ISSN 1401-7431, Vol. 35, no 3, 207-211 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Knowledge about myocardial metabolism in diabetic patients is limited, and even more so in association with myocardial ischaemia and cardiac surgery. This study investigates myocardial substrate utilization in type II diabetic patients after elective coronary artery bypass graft surgery (CABG).

DESIGN: Myocardial substrate utilization in 10 type II diabetic patients was assessed during the first hours after elective CABG with the coronary sinus catheter technique.

RESULTS: No significant myocardial uptake of carbohydrates was observed. Free fatty acids were extracted throughout the study period but uptake was not related to arterial levels. As arterial levels of beta-hydroxybutyric acid tended to increase a significant myocardial uptake emerged. The average extraction rate of beta-hydroxybutyric acid was 31% with a peak of 42%. A comparable extraction rate of glutamate was also found whereas alanine was released from the heart.

CONCLUSION: Free fatty acids were the main source of energy for the heart whereas uptake of carbohydrates was restricted. The high extraction rates of beta-hydroxybutyric acid and glutamate suggest an adaptive role for these substrates during this unfavourable metabolic state for the post-ischaemic diabetic heart.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13693 (URN)10.1080/140174301750305108 (DOI)
Available from: 2001-10-11 Created: 2001-10-11 Last updated: 2009-08-21
2. Effects of high-dose glucose–insulin–potassium on myocardial metabolism after coronary surgery in patients with Type II diabetes
Open this publication in new window or tab >>Effects of high-dose glucose–insulin–potassium on myocardial metabolism after coronary surgery in patients with Type II diabetes
Show others...
2001 (English)In: Clinical Science, ISSN 0143-5221, Vol. 101, no 1, 37-43 p.Article in journal (Refereed) Published
Abstract [en]

The effects of glucose–insulin–potassium (GIK) on cardiac metabolism have been studied previously in non-diabetic patients after cardiac surgery. Although patients with diabetes mellitus can be expected to benefit most from such treatment, the impact of GIK in diabetic patients undergoing cardiac surgery remains unexplored. Therefore the present study investigates the effects of high-dose GIK on myocardial substrate utilization after coronary surgery in patients with Type II diabetes. A total of 20 patients with Type II diabetes undergoing elective coronary surgery were randomly allocated to either post-operative high-dose GIK or standard post-operative care, including insulin infusion if necessary to keep blood glucose below 10 mmol/l. Myocardial substrate utilization was studied using the coronary sinus catheter technique. Haemodynamic state was assessed with the aid of Swan–Ganz catheters. High-dose GIK caused a shift towards carbohydrate utilization, with significant lactate uptake throughout the study period and significant uptake of glucose after 4 h. Arterial levels of non-esterified fatty acids and b-hydroxybutyric acid decreased, and after 1 h no significant uptake of these substrates was found. Increases in the cardiac index and stroke volume index were found in patients treated with high-dose GIK. A decrease in systemic vascular resistance was found both in the control group and in the high-dose GIK group. We conclude that high-dose GIK can be used in diabetic patients after cardiac surgery to promote carbohydrate uptake at the expense of non-esterified fatty acids and b-hydroxybutyric acid. This could have implications for treatment of the diabetic heart in association with surgery and ischaemia.

Keyword
coronary surgery, diabetes, glucose, b-hydroxybutyric acid, insulin, lactate, myocardial metabolism, non-esterified fatty acids, potassium
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13694 (URN)10.1042/CS20010005 (DOI)
Available from: 2001-10-11 Created: 2001-10-11 Last updated: 2009-08-21
3. Neurological injury after surgery for ischemic heart disease: risk factors, outcome and role of metabolic interventions
Open this publication in new window or tab >>Neurological injury after surgery for ischemic heart disease: risk factors, outcome and role of metabolic interventions
2001 (English)In: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, ISSN 1010-7940, Vol. 19, no 5, 611-618 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: Neurological complication remains a feared and increasing problem in association with cardiac surgery. The aim of this study was to analyze risk factors for neurological complications in a cohort of patients in whom inotropes for weaning from cardiopulmonary bypass was gradually replaced by metabolic treatment.

Methods: The records of 775 consecutive patients undergoing coronary artery bypass grafting (CABG) or combined CABG+valve procedures were examined. Forward stepwise multiple logistic regression analysis was used for statistical evaluation of independent risk factors.

Results: The incidence of neurological injury was 1.8% in patients undergoing isolated CABG and 5.4% after combined CABG+valve procedures. After cross-validation multivariate analysis identified history of cerebrovascular disease, advanced age and aortic cross-clamp time as independent risk factors for postoperative cerebral complications. Chronic obstructive pulmonary disease and number of bypasses also emerged as risk factors in the primary analysis.

Conclusions: In general, markers for advanced atherosclerosis, with history of cerebrovascular disease as the most important, emerged as predictors for neurological injury. Although it did not enter the final risk model, the results also suggest that postoperative heart failure deserves further surveillance as a potential risk factor for neurological complications. However, no evidence for untoward neurological effects associated with glutamate or glucose–insulin–potassium treatment was found.

Keyword
Neurological injury, Atherosclerosis, Cerebrovascular disease, Postoperative complications, Glutamate, Glucose, Cardiac surgery
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13695 (URN)10.1016/S1010-7940(01)00664-9 (DOI)
Available from: 2001-10-11 Created: 2001-10-11 Last updated: 2009-08-21
4. High-dose glucose-insulin-potassium after cardiac surgery: a retrospective analysis of clinical safety issues
Open this publication in new window or tab >>High-dose glucose-insulin-potassium after cardiac surgery: a retrospective analysis of clinical safety issues
2003 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, Vol. 47, no 4, 383-390 p.Article in journal (Refereed) Published
Abstract [en]

Background: Metabolic treatment with insulin or glucose-insulin-potassium (GIK) has received attention in association with myocardial infarction, cardiac surgery and critical care. As a result of insulin resistance during neuroendocrine stress, doses of insulin up to 1 IU kg−1 b.w.*h are required to achieve maximal metabolic effects after cardiac surgery. The clinical experience with regard to safety issues of such a high-dose GIK regime in critically ill patients after cardiac surgery is reported.

Methods: Retrospective, observational study involving all patients treated with high-dose GIK after cardiac surgery during one year in a cardiovascular center at a University Hospital.

Results: Eighty-nine patients out of 854 adult patients undergoing cardiac surgery were treated with high-dose GIK. Mean age was 69 ± 1 years, Higgins score 5.3 ± 0.3. Preoperatively 31.4% had left ventricular function EF≤0.35 and 32.5% had sustained a myocardial infarct during surgery. Mortality was 5.6% and the average ICU stay was 3.7 ± 0.5 days. The main indication for GIK was intraoperative heart failure (69.7%). The average glucose infusion rate during the first 6 h was 4.22 ± 0.15 and 4.91 ± 0.14 mg kg−1 b.w.*min, respectively, in diabetic and non-diabetic patients (P = 0.023). Blood glucose and s-potassium control was acceptable.

Conclusions: The high-dose GIK regime allowed substantial amounts of glucose to be infused both in diabetic and critically ill patients with maintenance of acceptable blood glucose control. Provided careful monitoring, this regime can be safely used in clinical practice and deserves further evaluation for treatment of critically ill patients following cardiac surgery.

Keyword
Cardiac surgery, glucose, insulin, metabolic support, myocardial infarction, postoperative heart failure, potassium, safety
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13696 (URN)10.1034/j.1399-6576.2003.00082.x (DOI)
Available from: 2001-10-11 Created: 2001-10-11 Last updated: 2009-08-21
5. Early postoperative outcome and medium-term survival in 540 diabetic and 2239 nondiabetic patients undergoing coronary artery bypass grafting
Open this publication in new window or tab >>Early postoperative outcome and medium-term survival in 540 diabetic and 2239 nondiabetic patients undergoing coronary artery bypass grafting
2002 (English)In: The Annals of Thoracic Surgery, ISSN 0003-4975, Vol. 74, no 3, 712-719 p.Article in journal (Refereed) Published
Abstract [en]

Background: An increasing proportion of patients undergoing coronary artery bypass grafting (CABG) are diabetics. Patient characteristics, early postoperative outcome, and midterm survival in diabetic patients after CABG were investigated.

Methods: A total of 2779 consecutive patients undergoing isolated CABG during 1995 to 1999 were studied, 19.4% of whom had diabetes mellitus. Demographic and peri-procedural data were registered prospectively in a computerized institutional database.

Results: The diabetic group was younger and included a higher proportion of women, and patients with hypertension, triple-vessel disease, and unstable angina. They required a higher number of bypasses, and longer cross-clamp and cardiopulmonary bypass times. Intensive care unit and hospital stays were prolonged and the need for inotropic agents, hemotransfusions, and dialysis was higher in the diabetic group. Renal failure, stroke (4.3% versus 1.7%), mediastinitis, and wound infections were more frequently encountered. Thirty-day mortality was 2.6% versus 1.6% (p = 0.15). Cumulative 5-year survival was 84.4% versus 91.3% (p < 0.001).

Conclusions: Short-term mortality was acceptable in diabetic patients after CABG but they had increased postoperative morbidity in comparison with nondiabetic patients, particularly with regard to renal function, cerebral complications, and infections. Midterm survival was impaired in diabetic patients mainly because of a less favorable outcome in patients treated with insulin.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13697 (URN)10.1016/S0003-4975(02)03778-5 (DOI)
Available from: 2001-10-11 Created: 2001-10-11 Last updated: 2009-11-01

Open Access in DiVA

fulltext(354 kB)896 downloads
File information
File name FULLTEXT01.pdfFile size 354 kBChecksum MD5
a1ba578dbee48c628b45e3afbb4fa4e182a3eaeccb4492a53642c5205038468650c033b9
Type fulltextMimetype application/pdf

Authority records BETA

Szabó, Zoltán

Search in DiVA

By author/editor
Szabó, Zoltán
By organisation
Thoracic SurgeryFaculty of Health SciencesDepartment of Thoracic and Vascular Surgery
Surgery

Search outside of DiVA

GoogleGoogle Scholar
Total: 896 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 600 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf