Early Donor Management Increases the Retrieval Rate of Lungs for Transplantation

University of Birmingham, Birmingham, England, United Kingdom
The Annals of thoracic surgery (Impact Factor: 3.85). 02/2008; 85(1):278-86; discussion 286. DOI: 10.1016/j.athoracsur.2007.07.092
Source: PubMed


Lung transplantation activity is frustrated by donor lung availability. We sought to examine the effect of active donor management and hormone administration on pulmonary function and yield in cadaveric heart-beating potential lung donors.
We studied 182 potential lung donors (arterial oxygen tension [PaO2]/fractional inspired oxygen [FIO2] ratio > or = 230). From this group, 60 patients (120 lungs) were allocated, within a randomized trial, to receive methylprednisolone (1 g), triiodothyronine (0.8 microg/kg bolus and 0.113 microg/kg/h infusion), both methylprednisolone and triiodothyronine, or placebo as soon as feasible after consent and initial assessment. Trial donors underwent protocol-guided optimization of ventilation and hemodynamics, lung water assessment, and bronchoscopy. Function was assessed by PaO2/FIO2 ratio, extravascular lung water index (EVLWI), and pulmonary vascular resistance (PVR). A nontrial group of 122 donors (244 lungs) received similar management without bronchoscopy, pulmonary artery flotation catheter monitoring, or lung water assessment.
Within the trial, management commenced within a median of 2 hours (interquartile range, 0.5 to 3.5 hours) of consent and continued for an average of 6.9 +/- 1.2 hours. The PaO2/FIO2 ratio deteriorated (p = 0.028) from 397 +/- 78 (95% CL, 376 to 417) to 359 +/- 126 (95% CL, 328 to 390) and EVLWI from 9.7 +/- 4.5 mL/kg (95% CL, 8.6 to 10.9 mL/kg) to 10.8 +/- 5.2 mL/kg (95% CL, 9.4 to 12.2 mL/kg; p = 0.009). PVR remained unchanged (p = 0.28). At end management, 48 of 120 trial lungs (40%) were transplanted versus 66 of 244 nontrial lungs (27%; p = 0.016). Neither methylprednisolone and triiodothyronine nor T3 increased lung yield or affected PaO2/FIO2 or EVLWI; however, methylprednisolone attenuated the increase in EVLWI (p = 0.009).
Early active management of lung donors increases yield. Steroid administration reduces progressive lung water accumulation.

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Available from: Jorge G Mascaro, Oct 13, 2015
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    • "Multiple large randomized control trials (RCT) have evaluated the effects on steroid administration on the outcomes of lung, kidney and liver transplant [35-37]. In a RCT, Bonser et al. evaluated the effects of 1g of methylprednisolone administration to BD organ donors 7 hours prior to lung explantation, demonstrating no effect on increasing lung yields [29]. Others in the realms of kidney transplantation have also failed to detect a significant improvement in the kidney survival at three months when 5g of methylprednisolone is administered to donors 2-4 hours prior to explantation. "
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    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.
    Journal of Translational Medicine 05/2014; 12(1):111. DOI:10.1186/1479-5876-12-111 · 3.93 Impact Factor
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    • "Currently, the use of corticosteroids in potential donors remains controversial, and there is no consensus regarding the time of the first administration or the ideal dose required to achieve an adequate anti-inflammatory effect 19. While several studies have shown that resuscitative hormonal protocols are promising, to date, no standard protocols for lung retrieval have been accepted 19-20. The use of corticosteroids in brain-dead donors is justified by two potential beneficial effects, namely a reduction in the inflammatory response and a replacement of the blood hormonal levels. "
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    ABSTRACT: Most lung transplants are obtained from brain-dead donors. The physiopathology of brain death involves hemodynamics, the sympathetic nervous system, and inflammatory mechanisms. Administering methylprednisolone 60 min after inducing brain death in rats has been shown to modulate pulmonary inflammatory activity. Our objective was to evaluate the effects of methylprednisolone on transplanted rat lungs from donors treated 60 min after brain death. Twelve Wistar rats were anesthetized, and brain death was induced. They were randomly divided into two groups (n = 6), namely a control group, which was administered saline solution, and a methylprednisolone group, which received the drug 60 min after the induction of brain death. All of the animals were observed and ventilated for 2 h prior to being submitted to lung transplantation. We evaluated the hemodynamic and blood gas parameters, histological score, lung tissue levels of thiobarbituric acid-reactive substances, level of superoxide dismutase, level of tumor necrosis factor-alpha, and level of interleukin-1 beta. After transplantation, a significant reduction in the levels of tumor necrosis factor-alpha and IL-1β was observed in the group that received methylprednisolone (p = 0.0084 and p = 0.0155, respectively). There were no significant differences in tumor necrosis factor-alpha and superoxide dismutase levels between the control and methylprednisolone groups (p = 0.2644 and p = 0.7461, respectively). There were no significant differences in the blood gas parameters, hemodynamics, and histological alterations between the groups. The administration of methylprednisolone after brain death in donor rats reduces inflammatory activity in transplanted lungs but has no influence on parameters related to oxidative stress.
    Clinics (São Paulo, Brazil) 02/2014; 69(2):128-33. DOI:10.6061/clinics/2014(02)09 · 1.19 Impact Factor
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    • "After initial measurements and BAL, donors received either T3, methylprednisolone, both T3 and MP or placebo (dextrose 5%) in a 1:1:1:1 randomization as previously described [12]. Details of blinding, randomization, donor management, a CONSORT flow diagram and hormonal group allocation outcomes for this trial have been previously reported [12]. Lung suitability for transplantation was predefined as an arterial PaO 2 / FiO 2 ≥300 mmHg immediately prior to retrieval without lung trauma, aspiration, infection or non-recruitable atelectasis being identified during assessment at direct inspection. "
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    ABSTRACT: Objectives: The measurement of extravascular lung water could aid the assessment and guide the management of potential lung donors following brain death. We therefore sought to validate a single indicator thermodilution extravascular lung water index (EVLWI-T) measurement using gravimetry and to assess the impact and clinical correlates of elevated EVLWI-T in potential lung donors and transplant recipients. Methods: In a prospective study, we measured serial EVLWI-T and haemodynamic and oxygenation data in 60 potential lung donors. To validate the EVLWI-T measurement, we measured in vivo thermodilution EVLWI (EVLWI-T) and gravimetric ex vivo EVLWI (EVLWI-G) in donor lungs rejected for transplant using the Holcroft and Trunkey modification of Pearce's method. We assessed the clinical correlates of elevated lung water and measured interleukin-8 and hepatocyte growth factor in bronchoalveolar lavage (BAL) fluid. Results: The mean EVLWI-T (n = 60) was 9.7 (4.5) ml kg(-1), being >7-10 ml kg(-1) in 23/60 and >10 ml kg(-1) in 16/60 potential donors. Donor lungs with EVLWI >10 ml kg(-1) were more likely to be receiving norepinephrine (P = 0.04), have higher pulmonary capillary wedge pressures (P = 0.008), be unsuitable for transplantation (P = 0.007) and, if transplanted, have worse survival (P = 0.04). Lungs submitted to gravimetric analysis [n = 20 in 11 donors (9 double and 2 single)] had EVWLI-T of 10.8 (2.7) and EVLWI-G was 10.1 (2.5). There was a strong correlation between EVLW-T and EVLW-G (r = 0.7; P = 0.014), but EVLWI-T over-predicted the EVLWI-G by ≈ 1 ml kg(-1) (EVLW-T = 1.05 × EVLW-G). Cytokine levels in BAL fluid were elevated. Conclusions: Elevated lung water is found in >50% of potential lung donors, predicts lung suitability for transplant and may adversely affect recipient outcome. Although EVLWI-T intrinsically overestimates gravimetric lung water, its measurement may aid the assessment of organ suitability. Lung water accumulation and the proinflammatory response may both be targets for modifying therapy.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 12/2012; 43(6). DOI:10.1093/ejcts/ezs657 · 3.30 Impact Factor
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