How does the methodological clinical evaluation impact organ donation? Experience from 4 Organ Procurement Organizations (OPO)

INTRODUCTION: The lack of a clear and reproducible methodology for evaluating potential organ donors, which ensures traceability in the process, can compromise the number of utilized organ donors and the transplantation quality. METHODOLOGY: We developed a reproducible and safe method for the evaluation and validation of Potential Organ Donors (PD) based on 2 principles:1) Updated knowledge of absolute contraindications for organ donation and, 2) Decision making supported by 3 questions. The first principle was absolute contraindications. They were categorized into 4 groups: A) Serologies, B) Tumors, C) Infections, and D) Biological risk for transmission of infectious diseases and cancer. The second principle was the decision-making questions: A) What is the cause of death? B) Are there absolute contraindications to organ donation? and, C) Are there relative contraindications to organ donation? Each PD was subjected to the same methodology. The questions were answered after knowing the PD's clinical file. The PD was valid only if the set of answers adhered to an established matrix respecting different guidelines. The same physician evaluated each PD in all OPO. We applied in 4 different OPO, 3 of them in the State of São Paulo/Brazil and one in the United Arab Emirates, in different periods, including the SARS-COV 2 pandemic. RESULTS: OPO­SCSP, before the methodology (2007): 62 utilized donors, 205 transplants. After the methodology has been started (2008/2009/2010): 117, 154, 186 utilized donors and 348, 533, 487 transplants, respectively. 2) OPO-BTU, before the methodology (2009): 9 utilized donors and 19 transplants. After the methodology has been started (2010/2011/2012): 17, 36, 49 utilized donors and 38, 90, 143 transplants, respectively. 3) OPO-IDPC, before the methodology (2017): 93 utilized donors and 202 transplants. After the methodology has been started (2018/2019/2020): 107, 177, 187 utilized donors and 219, 395, 356 transplants, respectively. 4) UAE OPO, before the methodology (2020): 9 utilized donors and 35 transplants. After the methodology has been started (2021/2022): 39, 55 utilized donors and 147, 203 transplants, respectively. The percentage increase after the beginning of the methodology, considering the last year evaluated: 1) OPO-SCSP: 195% (Utilized donors) and 137% (Transplants); 2) OPO-BTU: 444% (Utilized donors) and 652% (Transplants); C) OPO-IDPC: 101% (Utilized Donors) and 76% (Transplants); 4) OPO-EOTC (United Arab Emirates): 511% (Utilized donors) and 480% (Transplants). CONCLUSION: The methodology used demonstrates that it can directly contribute to increasing the percentage of effective donors and transplants. The increase in donors ranged from 101% to 444%. The percentage growth of transplantation ranged from 76% to 652%. Indirectly, an increase the referrals was observed, motivated by frequent contact with OPO members and ICU professionals.

Prospective, randomized, controlled, double-blind, multi-center, multinational study on the safety and efficacy of 6% Hydroxyethyl starch (HES) sOlution versus an Electrolyte solutioN In patients undergoing eleCtive abdominal Surgery: study protocol for the PHOENICS study.

BACKGROUND: Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss and to maintain hemodynamic stability. This study was requested by the European Medicines Agency (EMA) to provide more evidence on the long-term safety and efficacy of HES solutions in the perioperative setting. METHODS: PHOENICS is a randomized, controlled, double-blind, multi-center, multinational phase IV (IIIb) study with two parallel groups to investigate non-inferiority regarding the safety of a 6% HES 130 solution (Volulyte 6%, Fresenius Kabi, Germany) compared with a crystalloid solution (Ionolyte, Fresenius Kabi, Germany) for infusion in patients with acute blood loss during elective abdominal surgery. A total of 2280 eligible patients (male and female patients willing to participate, with expected blood loss ≥ 500 ml, aged > 40 and ≤ 85 years, and ASA Physical status II-III) are randomly assigned to receive either HES or crystalloid solution for the treatment of hypovolemia due to surgery-induced acute blood loss in hospitals in up to 11 European countries. The dosing of investigational products (IP) is individualized to patients' volume needs and guided by a volume algorithm. Patients are treated with IP for maximally 24 h or until the maximum daily dose of 30 ml/kg body weight is reached. The primary endpoint is the treatment group mean difference in the change from the pre-operative baseline value in cystatin-C-based estimated glomerular filtration rate (eGFR), to the eGFR value calculated from the highest cystatin-C level measured during post-operative days 1-3. Further safety and efficacy parameters include, e.g., combined mortality/major post-operative complications until day 90, renal function, coagulation, inflammation, hemodynamic variables, hospital length of stay, major post-operative complications, and 28-day, 90-day, and 1-year mortality. DISCUSSION: The study will provide important information on the long-term safety and efficacy of HES 130/0.4 when administered according to the approved European product information. The results will be relevant for volume therapy of surgical patients. TRIAL REGISTRATION: EudraCT 2016-002162-30 . ClinicalTrials.gov NCT03278548.

Recommendations for Perioperative Management of Patients with Cardiac Implantable Electronic Devices.

Four thousand cardiac implantable electronic devices (CIED) are implanted yearly in Croatia with constant increase. General anesthesia and surgery carry some specific risk for the patients with implanted CIEDs. Since most of the surgical procedures are performed in institutions without reprogramming devices available, or in the periods when they are unavailable, these guidelines aim to standardize the protocol for perioperative management of these patients. With this protocol, most of the procedures can be performed easily and, more importantly, safely in the majority of surgical patients.

Difficult airway management in a polytraumatized patient with osteogenesis imperfecta and multiple congenital spinal and thoracic deformities and severe kyphoscoliosis: case report.

Airway management in a polytraumatized patient with severe spinal and thoracic deformities demands detailed investigation of anatomical characteristics of the head, neck and airways, as well as thoracic configuration, before attempting endotracheal intubation. This enables the physician to predict a difficult airway and prepare for difficult airway management. We present a case of a 50-year-old polytraumatized patient with multiple congenital bone deformities associated with the syndrome of osteogenesis imperfecta and severe kyphoscoliosis, unable of lying on his back due to gibbus, who was successfully intubated in first attempt using video laryngoscope and only mild sedation. In patients with such severe multiple deformities, the use of video laryngoscope or Bonfils rigid endoscope should be mandatory in order to ensure success of intubation in first attempt and to avoid the possible aspiration of gastric contents.

Organ donation from a patient with bacterial meningoencephalitis -- the first case in Croatia.

The growing number of patients with terminal organ failure waiting for transplantation and the limited number of available organs demand that explantation teams see brain-dead patients with infectious diseases such as bacterial meningoencephalitis as potential donors, although until recently organ explantation from such donors has been contraindicated. This paper presents the first case of successful organ explantation from a donor with confirmed bacterial meningoencephalitis in our country. In this previously healthy patient (only with mild arterial hypertension in personal history), bacterial meningoencephalitis caused fulminant worsening and he deteriorated from mild disorder of consciousness (GCS 12) to brain death within only 24 hours. After the transplantation of organs was performed (heart, kidneys, liver and corneas were explanted), antibiotic therapy was continued in all organ recipients and two days after the transplantation none of the recipients showed any signs of infectious complications. This paper proves that this type of patients should also be treated as potential donors, under condition of appropriate microbiological diagnosis, antibiotic therapy and sustained hemodynamic stability, which should enlarge the number of organs available for transplantation.

Subclinical neurocognitive dysfunction after carotid endarterectomy-the impact of shunting.

BACKGROUND: Subclinical neurocognitive deficit after carotid endarterectomy (CEA) has been reported in 25% of patients. The influence of the type of anesthesia and shunting on early postoperative neurocognitive function remains unclear. Therefore, we analyzed the cognitive function after CEA using a battery of psychometric tests before surgery and on the first postoperative day. METHODS: Twenty nine patients under regional and 28 under general anesthesia were included in the study. Regional anesthesia was administered inducing a superficial cervical block, and the general anesthesia was induced using a standardized manner. Then cognitive function was tested using a battery of psychometric tests before and 24 hours after surgery. S 100 beta was determined at the same time points. RESULTS: A statistical difference was found between the results of the testing before and after CEA: decline in digit symbol test (9%), perceptual speed (6%), and spatial working memory (44%) and improvement in verbal fluency (6%) and attention (5%). The only intraoperative factor that correlated with the cognitive dysfunction was shunt insertion; patients with a shunt had a lower perceptual speed (P=0.005) and worse spatial working memory (P=0.004). No correlation was found between the type of anesthesia or S 100 beta level and any psychometric test, but these results might be influenced by the small sample size in our study. CONCLUSIONS: Shunt insertion was the only parameter correlated with cognitive decline on the first day after CEA. Regional anesthesia might offer indirect benefit because of a reduced need of shunting in wakeful patients. Larger studies are required to clarify the role of shunting and type of anesthesia in early neurocognitive deficit after CEA and its impact on the quality of life.

Obstruction of left ventricular outflow tract by a calcified mass at mitral valve.

A case of an unusual left ventricular outflow tract obstruction by mitral valve pathology in a 35-year old female with diabetes and end-stage renal disease is presented in the study. The patient suffered from fever of an unknown origin after lower-leg amputation. Although the wound healed well, fever persisted for three weeks despite a triple antibiotic treatment until the infection was resolved with vancomycin. Three months later echocardiography displayed a floating mass attached to mitral valve, producing a newly developed systolic murmur and a mild haemodynamic obstruction of the left ventricular outflow tract. The calcified vegetation was probably formed during an unrecognized subacute infective endocarditis.

Mechanism of postsystolic contraction and of multiple myocardial contractions during each single cardiac cycle.

Postsystolic contraction and other forms of phenomenon of multiple myocardial contractions are characterised by secondary or even tertiary contraction that follow regular one during each single cardiac cycle, triggered by a single sinus node impulse. These additional contractions occur at circumscribed areas of different myocardial regions, in many cardiac patients and healthy subjects. The mechanism of onset and perpetuation of the phenomenon is unknown. Our hypothesis is based on idea of existence of accessory, dead-end, slow-conducting, low-voltage pathways, derived from atrioventricular node or the bundle of His. Secondary contraction could occur in the following way: sinus node impulse divides into two pathways, the main atrioventricular conduction axis that depolarises the entire myocardium and the accessory pathway that depolarises again target region of myocardium where it ends blindly. Slow conduction through such accessory pathway enables a delay of secondary depolarisation needed to overcome the absolute refractory period of the myocardium following the 'regular' contraction. Electrocardiographic signal of a postsystolic potential is not visible at body surface because the pathway is low-voltage. The purpose of multiple myocardial contractions could be, although rarely, completing of current ejection, but more often, in the case of postsystolic contraction it could be a postsystolic tightening of the myocardium which would influence the regular contraction of the next cardiac cycle with the aim to reverse or prevent ventricular remodelling. In those circumstances, regional pathological function of ventricles (deformation of remodelled ventricle during the contraction, maybe during the relaxation as well, and furthermore asynchronous, but otherwise suboptimal contraction as well) would be detected by hypothetical myocardial receptors for strain and stretch, which would activate and sustain the function of accessory dead-end pathways by a neuroendocrine feed-back mechanism. The hypothesis is supported by anatomical findings of dead-end tracts originating from atrioventricular node and disappearing in the muscular part of interventricular septum. Extensive differences in the velocity of impulse propagation, which exist along the conduction system, allow the possibility that the accessory pathways are of slow-conducting properties. Low-amplitude signal of such pathways was confirmed by our intracardiac electrophysiological recording. Feed-back mechanism based on myocardial receptors for strain and stretch is a relevant option, keeping in mind well-known receptor based regulatory mechanisms across the cardiovascular system. The phenomenon is easily detectible, but hard to explain, so even considering herein presented hypothesis implies a need for change of settled perception of myocardial kinetics, and of physiological and pathological function of conducting system.

Spectrum of phenomena of multiple myocardial contractions during each single cardiac cycle.

The phenomenon of multiple myocardial contractions during each single cardiac cycle, triggered by a single sinus node impulse, is the most intriguing echocardiographical topic among detectible modalities of irregular kinetics of interventricular septum. Tissue Doppler imaging based methods gave proofs of active contractions in cases presented herein. Broad spectrum of this phenomenon, which can be found both in healthy subjects and in patients is presented. Forms of multiple myocardial contractions during the same cardiac cycle presented in this analysis are: secondary systolic contraction, postsystolic and late postsystolic contraction, multiple (three- and fourfold) contractions with combination of secondary systolic and postsystolic contraction, and combination of regular systolic, secondary systolic or postsystolic contraction with pre-contraction as a part of possible preexcitation. Explanation of mechanism generating these phenomena could be found in possible existence of accessory, concealed slow pathways of cardiac conduction system.

Successful conversion of recent-onset atrial fibrillation by sequential administration of up to three antiarrhythmic drugs.

BACKGROUND: Short-term conversion attempt of recent-onset atrial fibrillation (AF) in the emergency room fails too often. Many patients and doctors still prefer pharmacological to electrical solutions in such cases. HYPOTHESIS: Sequential administration of up to 3 antiarrhythmic drugs of different classes of action (amiodarone, propafenone, and quinidine) may achieve conversion in such patients. METHOD: One hundred and forty consecutive patients with recent-onset AF were transferred to the intensive cardiac care unit after a failed 2-h conversion attempt in the emergency room. First-line drug for conversion was continued up to a full dose, and was chosen by AF etiology, or in recurrent AF episodes, empirically. In nonresponders, the failed drug was replaced by a drug of another class, and if the second-line drug failed it was replaced by a drug of the third-line. Electrical cardioversion was the final solution for nonresponders. RESULTS: Sixty percent of patients reached sinus rhythm by the first-line drug therapy, 34% by the second-line, and 4% by the third-line. Seventy-five percent of patients achieved conversion within 26 h, and 95% of patients achieved conversion within 40 h. Three patients were electrically cardioverted due to hemodynamical instability. Two episodes of Torsade de Pointes ventricular tachycardia were self-terminated. CONCLUSION: Sequential usage of up to 3 antiarrhythmic drugs of different classes of action provides almost complete success in conversion of recent-onset AF in patients refractory to short-term conversion attempt in the emergency room.

Unremitting embolus from cardiac myxoma at circumflex artery trifurcation.

Embolisation of coronary artery from cardiac myxoma is very rare and it is not clear what happens with embolic material inside coronary artery after myocardial infarction. The natural course of myxomatous embolus is important because it determines the mode of surgical intervention. Different options of the course of embolus have been speculated, from spontaneous resorption to growth at artery wall. We report a case of embolisation of the circumflex artery trifurcation from a villous left atrial myxoma. The course of the embolus was displayed by coronary angiography repeated 6 months after myocardial infarction. Unlike the previously published case report, we found the embolus to be unremitting.