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Zirpe K, Pandit R, Gurav S, Mani RK, Prabhakar H, Clerk A, Wanchoo J, Reddy KS, Ramachandran P, Karanth S, George N, Vaity C, Shetty RM, Samavedam S, Dixit S, Kulkarni AP. Management of Potential Organ Donor: Indian Society of Critical Care Medicine-Position Statement. Indian J Crit Care Med 2024; 28:S249-S278. [PMID: 39234232 PMCID: PMC11369920 DOI: 10.5005/jp-journals-10071-24698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 03/18/2024] [Indexed: 09/06/2024] Open
Abstract
This position statement is documented based on the input from all contributing coauthors from the Indian Society of Critical Care Medicine (ISCCM), following a comprehensive literature review and summary of current scientific evidence. Its objective is to provide the standard perspective for the management of potential organ/tissue donors after brain death (BD) in adults only, regardless of the availability of technology. This document should only be used for guidance only and is not a substitute for proper clinical decision making in particular circumstances of any case. Endorsement by the ISCCM does not imply that the statements given in the document are applicable in all or in a particular case; however, they may provide guidance for the users thus facilitating maximum organ availability from brain-dead patients. Thus, the care of potential brain-dead organ donors is "caring for multiple recipients." How to cite this article Zirpe K, Pandit R, Gurav S, Mani RK, Prabhakar H, Clerk A, et al. Management of Potential Organ Donor: Indian Society of Critical Care Medicine-Position Statement. Indian J Crit Care Med 2024;28(S2):S249-278.
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Affiliation(s)
- Kapil Zirpe
- Department of Neurotrauma Unit, Grant Medical Foundation, Pune, Maharashtra, India
| | - Rahul Pandit
- Department of Critical Care, Fortis Hospital, Mumbai, Maharashtra, India
| | - Sushma Gurav
- Department of Neurotrauma Unit, Grant Medical Foundation, Pune, Maharashtra, India
| | - RK Mani
- Department of Critical Care and Pulmonology, Yashoda Super Specialty Hospital, Ghaziabad, Uttar Pradesh, India
| | - Hemanshu Prabhakar
- Department of Anesthesia, All India Institute of Medical Sciences, New Delhi, India
| | - Anuj Clerk
- Department of Intensive Care, Sunshine Global Hospital, Surat, Gujarat, India
| | - Jaya Wanchoo
- Department of Neuroanesthesia and Critical Care, Medanta The Medicity, Gurugram, Haryana, India
| | | | | | - Sunil Karanth
- Department of Critical Care Medicine, Manipal Hospital, Bengaluru, Karnataka, India
| | - Nita George
- Department of Critical Care Medicine, VPS Lakeshore Hospital & Research Center Kochi, Kerala, India
| | - Charudatt Vaity
- Department of Intensive Care, Fortis Hospital, Mumbai, Maharashtra, India
| | - Rajesh Mohan Shetty
- Department of Critical Care Medicine, Manipal Hospital, Bengaluru, Karnataka, India
| | - Srinivas Samavedam
- Department of Critical Care, Ramdev Rao Hospital, Hyderabad, Telangana, India
| | - Subhal Dixit
- Department of Critical Care Medicine, Sanjeevan & MJM Hospital, Pune, Maharashtra, India
| | - Atul P Kulkarni
- Department of Critical Care Medicine, Tata Memorial Centre, Mumbai, Maharashtra, India
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Hyun J, Lee SE, Kim JJ. Management of potential cardiac donors. CLINICAL TRANSPLANTATION AND RESEARCH 2024; 38:37-45. [PMID: 38725181 PMCID: PMC11075817 DOI: 10.4285/ctr.23.0065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 02/27/2024] [Accepted: 03/11/2024] [Indexed: 05/14/2024]
Abstract
Heart transplantation (HTx) outcomes have improved with careful donor selection and management; nonetheless, donor shortages remain a major challenge. Optimizing donor management is crucial for improving donor utility rates and post-HTx outcomes. Brain death leads to various pathophysiological changes that can affect multiple organs, including the heart. Understanding these alterations and corresponding management strategies is key to optimizing the donor organ condition. This review assesses several aspects of these pathophysiological changes, including hemodynamic and endocrinological considerations, and emphasizes special consideration for potential cardiac donors, including serial echocardiographic evaluations for reversible cardiac dysfunction and coronary assessments for donors with risk factors.
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Affiliation(s)
- Junho Hyun
- Division of Cardiology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang Eun Lee
- Division of Cardiology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae-Joong Kim
- Division of Cardiology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Dhar R, Marklin GF. Intravenous Levothyroxine for Unstable Brain-Dead Heart Donors. Reply. N Engl J Med 2024; 390:575-576. [PMID: 38324496 DOI: 10.1056/nejmc2314959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/09/2024]
Affiliation(s)
- Rajat Dhar
- Washington University School of Medicine, St. Louis, MO
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Akbaş T, Öztürk A. Alterations in neuroendocrine axes in brain-dead patients. Hormones (Athens) 2023; 22:539-546. [PMID: 37736855 DOI: 10.1007/s42000-023-00489-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 09/13/2023] [Indexed: 09/23/2023]
Abstract
PURPOSE To identify changes in anterior pituitary gland hormone levels in brain-dead patients and alterations in free triiodothyronine (fT3), free thyroxine, cortisol, testosterone, and estradiol levels. METHODS Ten postmenopausal women and 22 men with brain death (BD) were included. The first blood sample for determination of hormones (pre-BD) was collected when the clinician observed the first signs of BD. The second blood sample (BD day) was drawn after BD certification. RESULTS Female patients exhibited lower follicle-stimulating hormone and prolactin levels pre-BD and luteinizing hormone, follicle-stimulating hormone, and prolactin levels on BD day than the age-matched controls. Male patients' sex hormone levels were similar to those of the age-matched controls, except for testosterone levels, which were low in both consecutive measurements. All gonadotropins and prolactin levels were above the tests' lower detection limits (LDLs), except for one male patient with gonadotropin levels below the LDLs of the tests. Estradiol levels in both sexes ranged from normal to elevated. FT3 levels were significantly decreased in the two measurements. Thyroid-stimulating hormone (TSH) levels were low in eight patients and all low TSH levels were above the test's LDL. The remaining patients had normal or elevated TSH levels. The median adrenocorticotropic hormone (ACTH) and cortisol levels were within normal limits. All cortisol and ACTH levels were above the tests' LDLs, except for one patient with ACTH levels below the LDL in both measurements. CONCLUSION This study supports the hypothesis that the anterior pituitary gland continues to function in the brain-dead state.
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Affiliation(s)
- Türkay Akbaş
- School of Medicine, Department of Internal Medicine, Division of Intensive Care, Düzce University, Merkez, Konuralp Yerleşkesi, Beciyörükler Mevkii, Düzce, Türkiye.
| | - Ayhan Öztürk
- Düzce University Department of Neurology, School of Medicine, Düzce University, Düzce, Türkiye
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Lazzeri C, Bonizzoli M, Guetti C, Fulceri GE, Peris A. Hemodynamic management in brain dead donors. World J Transplant 2021; 11:410-420. [PMID: 34722170 PMCID: PMC8529942 DOI: 10.5500/wjt.v11.i10.410] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 07/22/2021] [Accepted: 09/10/2021] [Indexed: 02/06/2023] Open
Abstract
Donor management is the key in the complex donation process, since up to 20% of organs of brain death donors (DBD) are lost due to hemodynamic instability. This challenge is made more difficult due to the lack of strong recommendations on therapies for hemodynamic management in DBDs and more importantly to the epidemiologic changes in these donors who are becoming older and with more comorbidities (marginal donors). In the present manuscript we aimed at summarizing the available evidence on therapeutic strategies for hemodynamic management (focusing on vasoactive drugs) and monitoring (therapeutic goals). Evidence on management in elderly DBDs is also summarized. Donor management continues critical care but with different and specific therapeutic goals since the number of donor goals met is related to the number of organs retrieved and transplanted. Careful monitoring of selected parameters (possibly including serial echocardiography) is the clinical tool able to guarantee the achievement and maintaining of therapeutic goals. Despide worldwide differences, norepinephrine is the vasoactive of choice in most countries but, whenever higher doses (> 0.2 mcg/kg/min) are needed, a second vasoactive drug (vasopressin) is advisable. Hormonal therapy (desmopressin, corticosteroid and thyroid hormone) are suggested in all DBDs independently of hemodynamic instability. In the single patient, therapeutic regimen (imprimis vasoactive drugs) should be chosen also according to the potential organs retrievable (i.e. heart vs liver and kidneys).
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Affiliation(s)
- Chiara Lazzeri
- Intensive Care Unit and Regional ECMO Referral Centre, Azienda Ospedaliero Universitaria Careggi, Florence 50134, Italy
| | - Manuela Bonizzoli
- Intensive Care Unit and Regional ECMO Referral Centre, Azienda Ospedaliero Universitaria Careggi, Florence 50134, Italy
| | - Cristiana Guetti
- Intensive Care Unit and Regional ECMO Referral Centre, Azienda Ospedaliero Universitaria Careggi, Florence 50134, Italy
| | - Giorgio Enzo Fulceri
- Intensive Care Unit and Regional ECMO Referral Centre, Azienda Ospedaliero Universitaria Careggi, Florence 50134, Italy
| | - Adriano Peris
- Intensive Care Unit and Regional ECMO Referral Centre, Azienda Ospedaliero Universitaria Careggi, Florence 50134, Italy
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Hypothalamic function in patients diagnosed as brain dead and its practical consequences. HANDBOOK OF CLINICAL NEUROLOGY 2021; 182:433-446. [PMID: 34266610 DOI: 10.1016/b978-0-12-819973-2.00029-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Some patients who have been diagnosed as "dead by neurologic criteria" continue to exhibit certain brain functions, most commonly, neuroendocrine functions. In this chapter, we review the pathophysiology of brain death that can lead either to neuroendocrine failure or to preserved neuroendocrine functioning. We review the evidence on continued hypothalamic functioning in patients who have been declared "brain dead," examine potential mechanisms that would explain these findings, and discuss how these findings create additional confounds for brain death testing. We conclude by reviewing the evidence for the management of hypothalamic-pituitary failure in the setting of brain death and organ transplantation.
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Swanson EA, Adams T, Patel MS, De La Cruz S, Hutchens M, Khush K, Sally MB, Niemann CU, Groat T, Malinoski DJ. Impact of Deceased Donor Management on Donor Heart Use and Recipient Graft Survival. J Am Coll Surg 2020; 231:351-360.e5. [PMID: 32562768 DOI: 10.1016/j.jamcollsurg.2020.05.025] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 05/06/2020] [Accepted: 05/07/2020] [Indexed: 01/07/2023]
Abstract
BACKGROUND Current risk-adjusted models used to predict donor heart use and cardiac graft survival from organ donors after brain death (DBDs) do not include bedside critical care data. We sought to identify novel independent predictors of heart use and graft survival to better understand the relationship between donor management and transplantation outcomes. STUDY DESIGN We conducted a prospective observational study of DBDs managed from 2008 to 2013 by 10 organ procurement organizations. Demographic data, critical care parameters, and treatments were recorded at 3 standardized time points during donor management. The primary outcomes measures were donor heart use and cardiac graft survival. RESULTS From 3,433 DBDs, 1,134 hearts (33%) were transplanted and 969 cardiac grafts (85%) survived after 684 ± 392 days of follow-up. After multivariable analysis, independent positive predictors of heart use included standard criteria donor status (odds ratio [OR] 3.93), male sex (OR 1.68), ejection fraction > 50% (OR 1.64), and partial pressure of oxygen to fraction of inspired oxygen ratio > 300 (OR 1.31). Independent negative predictors of heart use included donor age (OR 0.94), BMI > 30 kg/m2 (OR 0.78), serum creatinine (OR 0.83), and use of thyroid hormone (OR 0.78). As for graft survival, after controlling for known recipient risk factors, thyroid hormone dose was the only independent predictor (OR 1.04 per μg/h). CONCLUSIONS Modifiable critical care parameters and treatments predict donor heart use and cardiac graft survival. The discordant relationship between thyroid hormone and donor heart use (negative predictor) vs cardiac graft survival (positive predictor) warrants additional investigation.
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Affiliation(s)
- Elizabeth A Swanson
- Medical Scientist Training Program, Oregon Health & Science University, Portland, OR
| | - Tony Adams
- Department of Medicine, Division of Pulmonary & Critical Care Medicine, Oregon Health & Science University, Portland, OR
| | - Madhukar S Patel
- Department of Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada
| | | | - Michael Hutchens
- Operative Care Division, Section of Surgical Critical Care, Veterans Affairs Portland Health Care System, Portland, OR
| | - Kiran Khush
- Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford
| | - Mitchell B Sally
- Department of Surgery, Division of Trauma, Critical Care and Acute Care Surgery, Oregon Health & Science University, Portland, OR; Operative Care Division, Section of Surgical Critical Care, Veterans Affairs Portland Health Care System, Portland, OR
| | - Claus U Niemann
- Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA; Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Tahnee Groat
- Operative Care Division, Section of Surgical Critical Care, Veterans Affairs Portland Health Care System, Portland, OR
| | - Darren J Malinoski
- Department of Surgery, Division of Trauma, Critical Care and Acute Care Surgery, Oregon Health & Science University, Portland, OR; Operative Care Division, Section of Surgical Critical Care, Veterans Affairs Portland Health Care System, Portland, OR.
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Anwar ASMT, Lee JM. Medical Management of Brain-Dead Organ Donors. Acute Crit Care 2019; 34:14-29. [PMID: 31723901 PMCID: PMC6849043 DOI: 10.4266/acc.2019.00430] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 02/19/2019] [Accepted: 02/22/2019] [Indexed: 11/30/2022] Open
Abstract
With improving healthcare services, the demand for organ transplants has been increasing daily worldwide. Deceased organ donors serve as a good alternative option to meet this demand. The first step in this process is identifying potential organ donors. Specifically, brain-dead patients require aggressive and intensive care from the declaration of brain death until organ retrieval. Currently, there are no specific protocols in place for this, and there are notable variations in the management strategies implemented across different transplant centers. Some transplant centers follow their own treatment protocols, whereas other countries, such as Bangladesh, do not have any protocols for potential organ donor care. In this review, we discuss how to identify brain-dead donors and describe the physiological changes that occur following brain death. We then summarize the management of brain-dead organ donors and, on the basis of a review of the literature, we propose recommendations for a treatment protocol to be developed in the future.
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Affiliation(s)
- A S M Tanim Anwar
- Department of Nephrology, Dhaka Medical College Hospital, Dhaka, Bangladesh
| | - Jae-Myeong Lee
- Department of Acute Care Surgery, Korea University Anam Hospital, Seoul, Korea
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Hahnenkamp K, Böhler K, Wolters H, Wiebe K, Schneider D, Schmidt HHJ. Organ-Protective Intensive Care in Organ Donors. DEUTSCHES ARZTEBLATT INTERNATIONAL 2018; 113:552-8. [PMID: 27598872 DOI: 10.3238/arztebl.2016.0552] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Revised: 05/02/2016] [Accepted: 05/02/2016] [Indexed: 12/22/2022]
Abstract
BACKGROUND The ascertainment of brain death (the irreversible, total loss of brain function) gives the physician the opportunity to limit or stop further treatment. Alternatively, if the brain-dead individual is an organ donor, the mode of treatment can be changed from patient-centered to donationcentered. Consensus-derived recommendations for the organ-protective treatment of brain-dead organ donors are not yet available in Germany. METHODS This review is based on pertinent publications retrieved by a selective search in PubMed, and on the authors' clinical experience. RESULTS Brain death causes major pathophysiological changes, including an increase in catecholamine levels and a sudden drop in the concentration of multiple hormones, among them antidiuretic hormone, cortisol, insulin, and triand tetraiodothyronine. These changes affect the function of all organ systems, as well as the hemodynamic state and the regulation of body temperature. The use of standardized donor management protocols might well increase the rate of transplanted organs per donor and improve the quality of the transplanted organs. In addition, the administration of methylprednisolone, desmopressin, and vasopressin could be a useful supplement to treatment in some cases. Randomized controlled trials have not yet demonstrated either improved organ function or prolonged survival of the transplant recipients. CONCLUSION The evidence base for organ-protective intensive care is weak; most of the available evidence is on the level of expert opinion. There is good reason to believe, however, that the continuation of intensive care, in the sense of early donor management, can make organ transplantation more successful both by increasing the number of transplantable organs and by improving organ quality.
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Affiliation(s)
- Klaus Hahnenkamp
- Department of Anesthesiology and Intensive Care Medicine, University Medicine Greifswald, German Organ Transplantation Foundation, North-East Donor Region, Berlin, Department of General and Visceral Surgery, University Hospital Münster, Department of Thoracic and Cardiovascular Surgery, University Hospital Münster, Department of Anaesthesiology and Intensive Care, University Hospital Leipzig, Department of Transplant Medicine, University Hospital Münster
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Rebolledo RA, Van Erp AC, Ottens PJ, Wiersema-Buist J, Leuvenink HGD, Romanque P. Anti-Apoptotic Effects of 3,3',5-Triiodo-L-Thyronine in the Liver of Brain-Dead Rats. PLoS One 2015; 10:e0138749. [PMID: 26437380 PMCID: PMC4593580 DOI: 10.1371/journal.pone.0138749] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Accepted: 09/03/2015] [Indexed: 12/31/2022] Open
Abstract
Background Thyroid hormone treatment in brain-dead organ donors has been extensively studied and applied in the clinical setting. However, its clinical applicability remains controversial due to a varying degree of success and a lack of mechanistic understanding about the therapeutic effects of 3,3’,5-Triiodo-L-thyronine (T3). T3 pre-conditioning leads to anti-apoptotic and pro-mitotic effects in liver tissue following ischemia/reperfusion injury. Therefore, we aimed to study the effects of T3 pre-conditioning in the liver of brain-dead rats. Methods Brain death (BD) was induced in mechanically ventilated rats by inflation of a Fogarty catheter in the epidural space. T3 (0.1 mg/kg) or vehicle was administered intraperitoneally 2 h prior to BD induction. After 4 h of BD, serum and liver tissue were collected. RT-qPCR, routine biochemistry, and immunohistochemistry were performed. Results Brain-dead animals treated with T3 had lower plasma levels of AST and ALT, reduced Bax gene expression, and less hepatic cleaved Caspase-3 activation compared to brain-dead animals treated with vehicle. Interestingly, no differences in the expression of inflammatory genes (IL-6, MCP-1, IL-1β) or the presence of pro-mitotic markers (Cyclin-D and Ki-67) were found in brain-dead animals treated with T3 compared to vehicle-treated animals. Conclusion T3 pre-conditioning leads to beneficial effects in the liver of brain-dead rats as seen by lower cellular injury and reduced apoptosis, and supports the suggested role of T3 hormone therapy in the management of brain-dead donors.
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Affiliation(s)
- Rolando A. Rebolledo
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
- Physiopathology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
| | - Anne C. Van Erp
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | - Petra J. Ottens
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | | | - Henri G. D. Leuvenink
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
- * E-mail:
| | - Pamela Romanque
- Physiopathology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
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Affiliation(s)
- Eunmi Gil
- Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae Berm Park
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Steroid Anti-Inflammatory Effects Did Not Improve Organ Quality in Brain-Dead Rats. BIOMED RESEARCH INTERNATIONAL 2015; 2015:207534. [PMID: 26090389 PMCID: PMC4452233 DOI: 10.1155/2015/207534] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 04/08/2015] [Indexed: 01/02/2023]
Abstract
Effect of glucocorticoid administration on improving the outcomes of kidney and liver allografts has not been clearly elucidated. This study investigated the effect of prednisolone administration after onset of brain death (BD) on kidney and liver in a controlled rat model of BD. BD was induced in rats by inflating an epidurally placed balloon catheter. Animals were treated with saline or prednisolone (5, 12.5, or 22.5 mg/kg) one hour after the onset of BD. After 4 hours of BD, experiments were terminated and serum and tissues were collected. Tissue gene and protein expression were measured for markers of inflammation, apoptosis, and cellular stress response markers. Prednisolone caused a reduction of plasma levels of IL-6, while the tissue expression of IL-6, IL-1β, and MCP-1 in both kidney and liver were also reduced. Creatinine plasma levels, complement (C3) expression, HSP-70, HO-1, Bcl2/BAX ratio, and PMN influx did not significantly change in kidney nor liver. Plasma AST and LDH levels were increased in the prednisolone treated group. Our results demonstrate prednisolone can has an anti-inflammatory effect mediated through reducing serum circulating cytokines. However, this anti-inflammatory effect does not translate into improved kidney function and indeed was associated with increased liver injury markers.
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Champigneulle B, Charpentier J. Conséquences cardiovasculaires de la mort cérébrale et prise en charge pour prélèvement d’organe(s). MEDECINE INTENSIVE REANIMATION 2015. [DOI: 10.1007/s13546-015-1055-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Rebolledo R, Liu B, Akhtar MZ, Ottens PJ, Zhang JN, Ploeg RJ, Leuvenink HGD. Prednisolone has a positive effect on the kidney but not on the liver of brain dead rats: a potencial role in complement activation. J Transl Med 2014; 12:111. [PMID: 24884924 PMCID: PMC4018938 DOI: 10.1186/1479-5876-12-111] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2014] [Accepted: 04/25/2014] [Indexed: 12/29/2022] Open
Abstract
Background Contradictory evidence has been published on the effects of steroid treatments on the outcomes of kidney and liver transplantation from brain dead (BD) donors. Our study aimed to evaluate this disparity by investigating the effect of prednisolone administration on BD rats. Methods BD induction was performed in ventilated rats by inflating a Fogarty catheter placed in the epidural space. Prednisolone (22.5 mg/kg) was administered 30 min prior to BD induction. After four hours of determination of BD: serum, kidney and liver tissues samples were collected and stored. RT-qPCR, routine biochemistry and immunohistochemistry were performed. Results Prednisolone treatment reduced circulating IL-6 and creatinine plasma levels but not serum AST, ALT or LDH. Polymorphonuclear influx assessed by histology, and inflammatory gene expression were reduced in the kidney and liver. However, complement component 3 (C3) expression was decreased in kidney but not in liver. Gene expression of HSP-70, a cytoprotective protein, was down-regulated in the liver after treatment. Conclusions This study shows that prednisolone decreases inflammation and improves renal function, whilst not reducing liver injury. The persistence of complement activation and the negative effect on protective cellular mechanisms in the liver may explain the disparity between the effects of prednisolone on the kidney and liver of BD rats. The difference in the molecular and cellular responses to prednisolone administration may explain the contradictory evidence of the effects of prednisolone on different organ types from brain dead organ donors.
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Affiliation(s)
- Rolando Rebolledo
- Department of Surgery, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
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Nair-Collins M, Northrup J, Olcese J. Hypothalamic-Pituitary Function in Brain Death: A Review. J Intensive Care Med 2014; 31:41-50. [PMID: 24692211 DOI: 10.1177/0885066614527410] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2013] [Accepted: 12/12/2013] [Indexed: 11/16/2022]
Abstract
The Uniform Determination of Death Act (UDDA) states that an individual is dead when "all functions of the entire brain" have ceased irreversibly. However, it has been questioned whether some functions of the hypothalamus, particularly osmoregulation, can continue after the clinical diagnosis of brain death (BD). In order to learn whether parts of the hypothalamus can continue to function after the diagnosis of BD, we performed 2 separate systematic searches of the MEDLINE database, corresponding to the functions of the posterior and anterior pituitary. No meta-analysis is possible due to nonuniformity in the clinical literature. However, some modest generalizations can reasonably be drawn from a narrative review and from anatomic considerations that explain why these findings should be expected. We found evidence suggesting the preservation of hypothalamic function, including secretion of hypophysiotropic hormones, responsiveness to anterior pituitary stimulation, and osmoregulation, in a substantial proportion of patients declared dead by neurological criteria. We discuss several possible explanations for these findings. We conclude by suggesting that additional clinical research with strict inclusion criteria is necessary and further that a more nuanced and forthright public dialogue is needed, particularly since standard diagnostic practices and the UDDA may not be entirely in accord.
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Affiliation(s)
- Michael Nair-Collins
- Department of Behavioral Sciences and Social Medicine, Florida State University College of Medicine, Tallahassee, FL, USA
| | | | - James Olcese
- Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL, USA
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Venkateswaran RV, Steeds RP, Quinn DW, Nightingale P, Wilson IC, Mascaro JG, Thompson RD, Townend JN, Bonser RS. The haemodynamic effects of adjunctive hormone therapy in potential heart donors: a prospective randomized double-blind factorially designed controlled trial. Eur Heart J 2009; 30:1771-80. [DOI: 10.1093/eurheartj/ehp086] [Citation(s) in RCA: 99] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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Salim A, Martin M, Brown C, Inaba K, Roth B, Hadjizacharia P, Mascarenhas A, Rhee P, Demetriades D. Using thyroid hormone in brain-dead donors to maximize the number of organs available for transplantation. Clin Transplant 2007; 21:405-9. [PMID: 17488392 DOI: 10.1111/j.1399-0012.2007.00659.x] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The aggressive management of brain-dead (cadaveric) organ donors has been shown to increase organs available for transplantation. Some centers use hormone therapy with thyroid hormone (T(4)) in selected donors. The purpose of this study is to evaluate the effects of T(4) on organs available for transplantation. A policy of aggressive donor management was adopted at our trauma center in 1998. T(4) therapy is reserved for the hemodynamically unstable donors who require significant vasopressor support. The records of patients who successfully donated organs between January 2001 and December 2005 were reviewed. Organ donor demographics and whether T(4) was used was examined for each donor. T(4) was used in 96 of 123 donors (78%). Compared with donors who did not receive T(4), those that did were similar in age (32 +/- 14 vs. 38 +/- 21, p = 0.148), had more organs donated (3.9 +/- 1.7 vs. 3.2 +/- 1.7, p = 0.048), and had no differences in brain-death related complications. Despite the severe hemodynamic instability in the T(4) group, the number of organs harvested from this group was significantly more than in patients who did not receive T(4). The use of T(4) in this group may result in the increased salvage of transplantable organs.
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Affiliation(s)
- Ali Salim
- Division of Trauma and Critical Care, Department of Surgery, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
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20
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Abstract
Patients with severe brain injuries (as can result from trauma, subarachnoid hemorrhage, or brain tumor) are monitored closely by nursing staff. It's often the nurse who first recognizes clinical signs of decompensation and begins the process of determining whether the patient is a potential organ donor. When a person is declared brain dead, it's the nurse who maintains hemodynamic stability so that donor organs remain viable. It's therefore crucial for nurses to know how brain death is determined in adults and how potential organ donors are identified, and to know the major physiologic changes that occur upon brain death, as well as essential nursing interventions.
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Affiliation(s)
- Kathleen M Z Peiffer
- Master's program in nurse anesthesia, College of Nursing and Health Professions, Drexel University, Philadelphia, PA, USA.
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21
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Abstract
Brain death of the donor is an important risk factor influencing graft outcome. In addition to its nonspecific effects, it potentiates graft immunogenicity and increases host alloresponsiveness. Thus brain death in addition to other unspecific injuries such as organ procurement, preservation and consequences of ischemia/reperfusion injury, contributes towards the change of an inert organ to an immunological altered graft. Prior to engraftment, brain death initiates a cascade of molecular and cellular events including the release of proinflammatory mediators leading to cellular infiltrates. Those events may affect the incidence of both acute and chronic changes, developing and contributing to reduced graft survival. Consequently, strategies to reduce the immunogenicity or the pro-inflammatory status of the graft are becoming more attractive and might even help to improve organ quality and graft function.
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Affiliation(s)
- J Pratschke
- Department of Visceral and Transplantation Surgery, Universitätsmedizin Berlin, Campus Virchow, Augustenburgerplatz 1, D-13353 Berlin, Germany.
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Pérez-Blanco A, Caturla-Such J, Cánovas-Robles J, Sanchez-Payá J. Efficiency of triiodothyronine treatment on organ donor hemodynamic management and adenine nucleotide concentration. Intensive Care Med 2005; 31:943-8. [PMID: 15937679 DOI: 10.1007/s00134-005-2662-9] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2004] [Accepted: 05/04/2005] [Indexed: 10/25/2022]
Abstract
OBJECTIVE We compared hemodynamic values, oxygen utilization, and adenine nucleotide concentration in the extracted organs of brain-dead donors treated with triiodothyronine vs. standard support treatment. DESIGN Prospective, randomized, double-blind controlled study. PATIENTS We recruited 52 consecutive adult cadaveric organ donors. Inclusion criteria were diagnosis of brain-death, transplantation suitability, and family consent for donation; exclusion criterion was preexisting thyroid disease. INTERVENTIONS The treatment group (n=29) received an intravenous bolus of 1 microg/kg triiodothyronine followed by continuous perfusion at 0.06 microg/kg per hour, and controls (n=23) received 0.9% ClNa delivered over 270 min. Hemodynamics, tonometry, thyroid hormones, and serum lactate were measured every 90 min from brain death to extraction procedure. Biopsies were processed to determine adenine nucleotides concentration. RESULTS Hemodynamic measurements did not differ significantly in the two groups, and the inotrope dose could not be diminished after treatment. Thyrotropin levels increased from brain death to extraction procedure in controls. Thyrotropin measured 90 and 180 min after the beginning of the perfusion was significantly lower in the treatment group than controls. The Pco2 gap increased in both groups from brain death to the extraction procedure. The lactate level of the treatment group was lower than in controls. Biopsy specimens were obtained in 19 controls and in 20 donors of the treatment group; the adenine nucleotides concentration did not show any significant difference. CONCLUSIONS Triiodothyronine did not add any benefit over the standard management of the organ donor nor did it affect the adenine nucleotides concentration of any biopsied organs.
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Affiliation(s)
- Alicia Pérez-Blanco
- Unidad de Cuidados Intensivos, Hospital General de Elda, Ctra. de Elda a Sax, 03600 Elda Alicante, Spain.
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23
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Abstract
The shortage of organ donors has become a serious problem in modern medicine. Room for improvement exists in our ability to convert potential donors to actual donors based on the available numbers and a significant amount of recent research. A significant percentage of the potential donors represent head-injured patients, so a significant amount of responsibility falls on surgeons to optimize the opportunity for donation. There are clear steps along the pathway from potential to actual donor where physicians can have a significant effect on the rate of successful donation: 1. Identify all potential donors and institute a review system to verify that all potential donors are being identified in your area. 2. Establish an acceptable method to rapidly and accurately determine brain death in potential donors using the local available services. 3. Approach all potential donor families for consent, decouple death notification and consent request, use a member of the hospital team and an OPO representative to approach the family, and make the request in a private setting. 4. Use an aggressive, proactive approach to the medical management of the potential donor using the techniques described to limit the number of medical failures and maximize the number of organs donated per donor. Institute a review process to evaluate any medical failures that occur. Given the difference between the numbers of potential versus actual donors, the authors' significant contact with potential donors, and the clear opportunities for improvement in their approach, the surgical community must address these issues surrounding the optimal management of potential donors and their families.
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Affiliation(s)
- T Razek
- Division of Trauma and Surgical Critical Care, Hospital of the University of Pennsylvania, Philadelphia, USA
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24
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Whitesall SE, Mayor GH, Nachreiner RF, Zwemer CF, D'Alecy LG. Acute administration of T3 or rT3 failed to improve outcome following resuscitation from cardiac arrest in dogs. Resuscitation 1996; 33:53-62. [PMID: 8959774 DOI: 10.1016/s0300-9572(96)00985-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Documentation of profound changes in serum thyroid hormone concentrations associated with cardiac arrest and resuscitation, as well as other acute emergencies, have spurred evaluation of possible therapeutic thyroid hormone administration. Acute and significant, this state, characterized by abnormally low serum thyroid hormone concentrations, may indicate selective thyroid replacement therapy. In a previous investigation, post-resuscitation infusion of levothyroxine sodium (L-T4) to normalize serum 3,5,3'-triiodothyronine (T3) concentrations was associated with significant reduction of neurologic deficit caused by severe global cerebral ischemia. Since L-T4 has been reported to act directly or via one of its metabolites, most likely T3, this most active form of thyroid hormone was tested. When L-T4 reduced the neurologic deficit, an increase in 3,3',5'-triiodothyronine (rT3) was also observed. This study therefore determined whether a post-resuscitation treatment with either T3 (n = 8) or rT3 (n = 8) provided protection against global cerebral ischemia comparable to that of L-T4. Global cerebral ischemia was achieved with 9 min of ventricular fibrillation. Following resuscitation, one of three solutions (saline group as a control) was infused for 24 h at rates that reproduced the normal serum T3 concentrations or the rT3 concentrations achieved previously during the L-T4 therapy. The successful elevation of T3 and mimicking rT3 concentrations was assessed and confirmed by radioimmunoassay (RIA). In addition, TSH levels were measured by a novel RIA specific for canine thyroid-stimulating hormone (cTSH). Neurologic deficit was assessed with a well-standardized neurologic deficit examination. In contrast to previous studies using L-T4 infusion, no significant reduction of neurologic deficit was observed. Serum thyroid hormone changes confirmed previously described decreases and in no case did changes in cTSH appear causal in these changes. Thus, we concluded that L-T4 may offer a therapeutic advantage over T3 or rT3.
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Affiliation(s)
- S E Whitesall
- Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622, USA
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25
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The potential role of thyroid hormone substitutes in cardiac surgery and transplantation. ACTA ACUST UNITED AC 1996. [DOI: 10.1016/s1324-2881(96)90013-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Bittner HB, Kendall SW, Chen EP, Van Trigt P. Endocrine changes and metabolic responses in a validated canine brain death model. J Crit Care 1995; 10:56-63. [PMID: 7647843 DOI: 10.1016/0883-9441(95)90017-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
PURPOSE Endocrinologic and metabolic changes after brain death (BD) have not yet been investigated in a validated animal model. Therefore, the effects of BD on hormonal and metabolic function were studied in 10 dogs (23 to 31 kg). METHODS BD was induced by intracranial pressure increase and validated neuropathologically. Plasma concentrations of pituitary, thyroid, adrenal, and pancreatic hormones were measured pre/post BD. The results are expressed as mean (+/- SEM). RESULTS A Cushing reflex and diabetes insipidus occurred after BD. Elevated catecholamine levels were documented after 15 minutes whereas the pituitary gland hormones vasopressin and adrenocorticotrophic hormone (ACTH) decreased significantly after 15 and 45 minutes of BD respectively. Thyroxine, triiodothyronine, and glucagon decreased significantly (P < .01) from 0.58 ng/mL (+/- 0.05), 2.20 micrograms/dL (+/- 0.15), and 49.7 pg/mL (+/- 9.1) respectively to 0.34 ng/mL (+/- 0.03), 1.14 micrograms/dL (+/- 1.14), and 6.9 pg/mL (+/- 1.4) respectively 420 minutes after BD. The hematocrit increased significantly after BD and declined toward the end of all experiments. Metabolic acidosis occurred immediately after BD and at the end of the experiments. CONCLUSIONS In a simple, reproducible, and reliable animal model of BD, a catecholamine storm, vasopressin and ACTH cessation, and diabetes insipidus were consistent findings. The decrease in cortisol and vasopressin levels warrant consideration of hormonal therapy.
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Affiliation(s)
- H B Bittner
- Department of General and Cardiothoracic Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA
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27
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Mokken FC, Henny CP, Kedaria M, Gelb AW. Hemorrheological changes associated with brain death and their implications for potential organ donors. Transpl Int 1995. [DOI: 10.1111/j.1432-2277.1995.tb01490.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Mokken FC, Henny CP, Kedaria M, Gelb AW. Hemorrheological changes associated with brain death and their implications for potential organ donors. Transpl Int 1995; 8:147-51. [PMID: 7766297 DOI: 10.1007/bf00344425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Successful transplantation of donor organs from brain-dead patients requires adequate maintenance of hemodynamic parameters. Blood flow and tissue perfusion are highly dependent upon hemorrheology. The aim of the present study was to evaluate hemorrheological parameters in potential organ donors compared to healthy volunteers. Whole blood-, plasma- and corrected blood viscosity, hematocrit, erythrocyte deformability, and erythrocyte aggregation were obtained in ten consecutive brain-dead patients and ten matched volunteers. Compared to controls, hematocrit and whole blood viscosity at high and medium shear rates and erythrocyte deformability were significantly decreased. Plasma viscosity was significantly increased in all patients. In the same group, a highly significant increase was observed at all shear rates when viscosity was corrected for hematocrit. Definite rheological abnormalities were found in the blood of brain-dead patients, something which might lead to impaired organ function after transplantation. Therefore, optimizing such parameters by special fluid management may be of importance in potential organ donors.
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Affiliation(s)
- F C Mokken
- Laboratory of Clinical Hemorrheology, University Hospital of the University of Amsterdam, The Netherlands
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29
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Facktor MA, Mayor GH, Nachreiner RF, D'Alecy LG. Thyroid hormone loss and replacement during resuscitation from cardiac arrest in dogs. Resuscitation 1993; 26:141-62. [PMID: 8290809 DOI: 10.1016/0300-9572(93)90174-o] [Citation(s) in RCA: 25] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Circulating concentrations of thyroxine (T4), triiodothyronine (T3), and reverse triiodothyronine (rT3) were followed in dogs subjected to 9 min of normothermic ventricular fibrillation. Significant decreases were detected 12 h post-arrest when compared to pre-arrest levels in total T4 (P < 0.0005), free T4 (P < 0.0005), total T3 (P < 0.003), and free T3 (P < 0.003), and levels of reverse T3 were significantly elevated (P = 0.0001). Similar changes occurred with only 30 s of arrest. Post-arrest replacement therapy with 7.5 micrograms/kg per h (Rx-7.5) and 15 micrograms/kg per h (Rx-15) levothyroxine sodium (L-T4) increased total T4, free T4, and total T3 (P < 0.01). Free T3 decreased in the Rx-7.5 group (P < 0.01) and did not fall in the Rx-15 group (P = 0.16). Reverse T3 increased with either treatment (P < 0.005). Both treatment groups had higher levels of all five hormones than non-treated animals (P < 0.001). Neurologic function, assessed with a standardized scoring system, showed significant improvement in the treated groups by 6 h (P < 0.05, compared to non-treated group) and remained significant through 24 h post-arrest (P < 0.05). The documentation of rapid and dramatic changes in thyroid hormones immediately following cardiac arrest and resuscitation indicates a significant acute hypothyroid state that may potentially benefit from replacement therapy.
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Affiliation(s)
- M A Facktor
- Department of Physiology, University of Michigan Medical School, Ann Arbor 48109
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30
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Wijnen RM, van der Linden CJ. Donor treatment after pronouncement of brain death: a neglected intensive care problem. Transpl Int 1991; 4:186-90. [PMID: 1958285 DOI: 10.1007/bf00335342] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The need for cadaveric organs for transplantation is increasing. To decrease the shortage of organs, identification of potential donors and conditioning of these donors must improve. We present a review of relevant data on body and tissue alterations due to brain death and summarize the recent literature covering experimental and clinical studies on optimal donor management.
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Affiliation(s)
- R M Wijnen
- Department of Surgery, University Hospital Maastricht, The Netherlands
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