Recommendations for the diagnosis and management of persons with suspected vaccine-induced immune thrombotic thrombocytopenia (VITT) / Recomendaciones para diagnostico y manejo de personas con trombocitopenia trombotica inmune inducida por vacunas (VITT)

Abstract In recent months, rare cases of thrombosis at unusual sites associated with thrombocytopenia, occurring within a typical risk window (i.e., 4-28 days) after receiving SARS CoV2 vaccines, have been reported. Healthcare professionals should be prepared to detect these cases on time. The Expert Panel of the Knowledge Management and Transfer Network conducted a free search of the related literature. With the available information and the clinical expertise of the working group, we formulated, reviewed, and endorsed recommendations for the timely suspicion, diagnosis (case definitions, the use of initial laboratory and imaging tests, specific tests), and management of these thrombotic conditions. This document is considered a living document that will be updated as new evidence emerges, and recommendations may change over time.

Resumen En meses recientes se han reportado casos raros de trombocitopenia y trombosis en sitios inusuales, que ocurren dentro de una ventana de riesgo típica ( por ejemplo de 4 a 28 días) luego de recibir vacunas de SARS CoV 2. Los profesionales de la salud deben estar preparados para detectar estos casos a tiempo. Un panel de expertos y una red de transferencia de conocimiento realizó una búsqueda libre de literatura seleccionada. Con la información disponible y la experticia clínica del grupo de trabajo revisamos y dimos recomendaciones para la sospecha temprana, el diagnostico (definición de caso, el uso de pruebas de laboratorio especificas y de imágenes diagnósticas) para le manejo de estas condiciones tromboticas. Este documento es considerado un documento vivo que debe ser actualizado a medida que surja nueva evidencia y las recomendaciones vayan cambiando con el tiempo

Cirugía citorreductiva y quimioterapia intraperitoneal hipertérmica: Conceptos importantes para el anestesiólogo / Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: main concepts for anesthetists

Abstract Introduction: Hyperthermic intraperitoneal chemotherapy (HIPEC) is a complex therapeutic procedure used to complement cytoreductive surgery and intravenous chemotherapy for the management of primary peritoneal neoplasms and peritoneal carcinomatosis. Objectives: To review considerations regarding the surgical procedure, physiological changes associated with fluid, blood and protein loss, increase in intra-abdominal pressure, metabolic rate, and systemic hyperthermia, from the perspective of the anesthetist. Methods: A nonsystematic search was conducted in the Medline/PUBMED and Google Academics databases using the terms cytoreductive surgery, hyperthermia, HIPEC, peritoneal carcinomatosis, and Sugarbaker. No limits for publication dates were used. The articles were reviewed independently by each of the authors, and the final text was edited and approved by the main author. Results: Overall, 151 articles were identified, and, of these, 64 were included in the review. The aspects studied included the surgical technique, physiological changes during the procedure, and anesthetic management. Conclusion: Cytoreductive surgery with hyperthermic intra-peritoneal chemotherapy is a therapeutic option for patients with peritoneal carcinomatosis. This procedure involves risks for the patient, first because of an initial phase which involves fluid and blood loss, and, second, because the hyperthermic phase gives rise to a hyperdynamic state with hemodynamic instability. Anesthetists must be familiar with the basic aspects of management to reduce complications and improve patient outcomes.

Resumen Introducción: La quimioterapia intraperitoneal hipertérmica (Hyperthermic Peritoneal Chemotherapy - HIPEC) es un procedimiento terapéutico complejo, utilizado como complemento de la cirugía citorreductiva (CCR) y de la quimioterapia endovenosa, para manejo de las neoplasias peritoneales primarias y la carcinomatosis peritoneal. Objetivos: Revisar desde la perspectiva del anestesiólogo, conceptos generales sobre el procedimiento quirúrgico, los cambios fisiológicos asociados a la pérdida de fluidos, sangre y proteínas, al aumento de la presión intra-abdominal, la tasa metabólica y la hipertermia sistémica. Métodos: Se realizó una búsqueda no sistemática en las bases de datos Medline/PUBMED y Google Academics utilizando los términos cytoreductive surgery, hyperthermia, HIPEC, peritoneal carcinomatosis y Sugarbaker. No se establecieron límites para fecha de publicación. Los artículos fueron revisados de manera independiente por cada uno de los autores y el texto final fue editado y aprobado por el autor principal. Resultados: Fueron identificados 151 artículos, de los cuales se incluyeron 64 para la revisión. Los aspectos estudiados incluyeron la técnica quirúrgica, los cambios fisiológicos durante el procedimiento y el manejo anestésico. Conclusión: La cirugía citorreductiva más quimioterapia intraperitoneal hipertérmica es una alternativa terapéutica para los pacientes con carcinomatosis peritoneal. Este procedimiento supone riesgos para el paciente, tanto por una primera fase que implica pérdidas de fluidos y sangre, como por la fase de hipertermia que genera un estado hiperdinámico con inestabilidad hemodinámica. El anestesiólogo debe conocer los aspectos fundamentales del manejo para disminuir las complicaciones y mejorar los desenlaces de los pacientes.

Solución salina hipertónica para modificar la lesión tisular por isquemia/reperfusión: modelo porcino de oclusión de aorta / Hypertonic saline solution for modifying tissue ischemia/reperfusion injury: Porcine aortic occlusion model

Abstract Introduction: Decreased blood flow disrupts the endothelium, changes the nitric oxide/endothelin -1 ratio, narrows the capillaries and results in microcirculatory dysfunction. Secondary anoxia leads to mitochondrial energy imbalance, depletion of adenosine-triphosphate and disruption of the intracellular hydrogen, sodium and calcium homeostasis. If the flow is restored, the reperfusion stimulates the endothelial expression of adhesion molecules attracting polymorphic nucleotides and platelets, with sub endothelial infiltration of these cells and their entrapment in the microvasculature, as well as vasoconstriction, endothelial edema and reduced flexibility of the cellular membrane. Ischemia/reperfusion may result in inflammation and organ failure. Objective: To determine whether hypertonic saline solution reduces the ischemic/reperfusion injury in the liver, the kidney, and the ileum. Materials and methods: Experimental trial in pigs. Aortic blood flow suppression (15 min) and reperfusion (60 min). The experimental group was pretreated with 7.5% hypertonic saline and the control group received normal 0.9% saline solution. Hemodynamic, gasometric, and biochemical measurements were taken, and the serum and tissue levels of ET-1, TNF-alpha, IL-10, and IL-2 were determined. Results: There were no significant differences in the tissue expression of ET-1, TNF-alpha, IL-10, and IL-2 between the two groups. The hemodynamic behavior was similar in both groups. The group treated with hypertonic solution showed an increasing post-perfusion systolic rate up to the basal values, while the systolic rate in the control group dropped significantly (p = 0.015). Conclusion: Hypertonic solution prior to the ischemic insult improves the ventricular function after reperfusion.

Resumen Introducción: La disminución del flujo sanguíneo altera el endotelio, cambia la relación óxido nítrico/endotelina-1, estrecha capilares y produce disfunción microcirculatoria. La anoxia secundaria lleva a desacople energético mitocondrial, depleción de adenosín-trifosfato y alteración de la homeostasis intracelular de hidrógeno, sodio y calcio. Si el flujo se reanuda, la reperfusión estimula la expresión endotelial de moléculas de adhesión que atraen polimorfonucleares y plaquetas, con infiltración subendotelial de estas células y su atrapamiento en la microvasculatura, así como vasoconstricción, edema endotelial y disminución de la flexibilidad de la membrana celular. La isquemia/reperfusión puede derivar en inflamación y fallo orgánico. Objetivo: Determinar si la solución salina hipertónica disminuye la lesión isquemia/reperfusión en hígado, riñón e íleon. Materiales y métodos: Estudio experimental en cerdos. Supresión del flujo sanguíneo aórtico (15 min) y reperfusión (60 min). El grupo experimental recibió pretratamiento con solución salina hipertónica al 7,5% y el grupo control solución salina normal al 0,9%. Se realizaron mediciones hemodinámicas, gasométricas, bioquímicas y determinación sérica y tisular de ET-1, TNF-alfa, IL-10, IL-2. Resultados: No hubo diferencias significativas en la expresión tisular de ET-1, TNF-alfa, IL-10, IL-2 entre los grupos. Los grupos presentaron un comportamiento hemodinámico similar. El grupo tratado con hipertónica exhibió un índice sistólico post-reperfusión que aumentó hasta los valores basales, mientras que el índice sistólico del grupo control presentó una caída significativa (p = 0,015). Conclusión: La solución hipertónica antes del insulto isquémico mejora la función ventricular después de la reperfusión.

Réplica a la Carta al Editor: Manual de práctica clínica basado en la evidencia: preparación del paciente para el acto quirúrgico y traslado al quirófano / Reply to the Letter to the Editor: Evidence based clinical practice manual: Patient preparation for surgery and transfer to the operating room theater

Reply to letter to the Editor

Manual de práctica clínica basado en la evidencia: preparación del paciente para el acto quirúrgico y traslado al quirófano / Evidence-based clinical practice manual: Patient preparation for surgery and transfer to the operating room

Introduction: Patient preparation for surgery and transfer to the operating room are two priority processes defined within the procedures and conditions for authorization of health care services by the Ministry of Social Protection in Colombia. Objectives: The aim of this initiative was to develop a manual of clinical management based on the evidence on patient preparation for surgery and transfer to the operating room. Materials and methods: A process divided into four phases (conformation of the development group, systematic review of secondary literature, participatory consensus method, and preparation and writing of the final document) was performed. Each of the standardized techniques and procedures is used to develop evidence-based manuals. Results: Evidence-based recommendations on pre-anaesthetic assessment, preoperative management of medical conditions, education and patient communication, informed consent, patient transfer to the surgical area, surgical site marking, strategies for infection prevention and checklist were performed. Conclusion: It is expected that with the use of this manual the incidence of events that produce morbidity and mortality in patients undergoing surgical procedures will be minimized.

Introducción: La preparación del paciente para el acto quirúrgico y el traslado del paciente al Quirófano son 2 procesos prioritarios definidos dentro de los procedimientos y condiciones de habilitación de servicios de salud por parte del Ministerio de Salud y la Protección Socialen Colombia. Objetivos: El objetivo de esta iniciativa fue desarrollar un manual de manejo clínico basado en la evidencia sobre la preparación del paciente para el acto quirúrgico y traslado al quirófano. Materiales y métodos: Se realizó un proceso dividido en 4 fases (conformación del grupo elaborador, revisión sistemática de literatura secundaria, método participativo de consenso, y preparación y escritura del documento final). Cada una de ellas usó técnicas y procedimientos estandarizados para el desarrollo de manuales basados en la evidencia. Resultados: Se realizaron recomendaciones basadas en la evidencia sobre valoración pre-anestésica, manejo preoperatorio de condiciones médicas, educación y comunicación con los pacientes, consentimiento informado, traslado del paciente al área quirúrgica, marcación del sitio quirúrgico, estrategias para la prevención de infecciones, y lista de chequeo preoperatorio. Conclusiones: Se espera que con el uso de este manual se minimice la incidencia de eventos que produzcan morbimortalidad en pacientes sometidos a procedimientos quirúrgicos.

Stroke volume response to liver graft reperfusion stress in cirrhotic patients.

INTRODUCTION: In patients with advanced cirrhosis, stressful stimuli may reveal a silent reduced cardiac performance. During liver transplantation (LT), graft reperfusion strongly stresses the heart and may unmask latent myocardial dysfunction. AIM: The objective of this study was to assess heart response to acutely increased preload after liver graft reperfusion and correlate this response with preoperative data and outcome. METHODS: Preoperative clinical, echocardiographic, and hemodynamic data, and patient outcome were retrospectively recorded for 235 liver recipients who had no known cardiac disease. Myocardial dysfunction was defined as less than 10 % increase of stroke volume after graft reperfusion (non-responder). RESULTS: We found 84 (35.7 %) non-responder patients. The non-responders showed higher Model for end-stage liver disease scores (p = 0.046), left atrial diameter (LAD) (p = 0.040), hepatic vein pressure gradient (p = 0.055), and hyperdynamic state than responders. The percentages of patients with hyponatremia (p = 0.048) and alcohol etiology (p = 0.025) were also higher among non-responders. Independent predictors of inadequate cardiac response in the multivariate analysis were low preoperative systemic vascular resistance (SVRI) [odds ratio (OR) 3.09, 95 % CI 1.15-4.82; p = 0.027] and enlargement of LAD (OR 2.08, 95 % CI 1.49-2.74; p = 0.044). Non-response was associated with higher rates of early cardiovascular events [hazard ratio (HR) 2.84, 95 % CI 1.09-4.22; p = 0.039] and higher length of intensive care unit stay (p = 0.038). No differences were found in 1-year survival rates. CONCLUSIONS: Latent cardiac dysfunction among LT recipients, considered to be abnormal stroke volume response to unclamping of portal vein, is very prevalent. SVRI and LAD were independent predictors of inadequate responses. This condition deserves special attention since it may aggravate the early postoperative course of LT.

Effect of intra-abdominal pressure on hepatic microcirculation: implications of the endothelin-1 receptor.

OBJECTIVE: To investigate the effect of endothelin receptor A (ET(A)) and endothelin receptor B (ET(B)) blockade on liver microcirculation and oxygenation during intra-abdominal pressure (IAP) increase. METHODS: Fifteen anesthetized pigs were randomized to receive either nonselective endothelin-1 (ET-1) blocker tezosentan (TG, n = 7) or saline (CG, n = 8). Helium was insufflated to increase IAP from 0 to 25 mmHg. Stroke volume variability was maintained ≤ 12% with colloid infusion. Total liver blood flow (TLBF), hepatic microcirculatory blood flow (MBF), hepatic tissue oxygenation (HpO(2)), hyaluronic acid and plasma disappearance rate (PDR) of indocyanine green (ICG) were recorded. RESULTS: TLBF remained mostly unaltered in both groups at low IAP and decreased only in CG at the IAP of 25 mmHg. As IAP increased, a significant decline in MBF was observed without correlation with cardiac output or TLBF. In CG, HpO(2) decreased as early as IAP of 10 mmHg to high levels of pressure. However, in TG the decrease was significant only at the IAP of 25 mmHg. PDR of ICG decreased in both groups at IAP of 25 mmHg (P = 0.046 and P = 0.009 in TG and CG, respectively). These changes correlated with MBF (r = 0.793). CONCLUSION: Blocking ET(A) and ET(B) receptors partially protects sinusoidal circulation and tissue oxygenation against stress induced by high IAP.

Reproducibility of Electronic Von Frey and Von Frey monofilaments testing.

OBJECTIVES: Von Frey monofilaments (VFM) and Electronic von Frey are used as quantitative sensory testing to explore mechanical hyperalgesia. The aim of the study was to determine VFM and Electronic von Frey reproducibility and the time required for testing undamaged areas in volunteers and surgical in-hospital patients. METHODS: Prospective study in 2 groups of individuals without neurological disorders and not receiving treatments that alter sensorial response. Group 1 was formed by 30 healthy volunteers and group 2 by 28 patients after knee arthroplasty who received unilateral femoral block as postoperative analgesia. Testing was performed by 2 trained investigators in the forearm and abdominal wall and repeated 24 hours later. Pain threshold was determined as the VMF or the pressure rate applied with the Electronic von Frey referred to as unpleasant. The time used in each test was measured. Intraobserver and interobserver reproducibility were analyzed by means of Kappa and Lin coefficients. RESULTS: Intraobserver and interobserver reproducibility for VFM was only fair or moderate in both groups (Kappa<0.6). Intraobserver reproducibility for Electronic von Frey was good in Group 1 (Lin 0.61 to 0.8) and almost perfect in Group 2 (Lin>0.8). No differences were found between the 2 tested areas. Time used was 6.03 and 3.16 minutes for VFM and Electronic von Frey, respectively. DISCUSSION: Exploration of mechanical allodynia in postoperative patients requires rapid and reliable quantitative sensory testing. Electronic von Frey was more reliable and rapid than VFM in exploring mechanical pain thresholds in undamaged areas in volunteers and patients. Further studies are required to confirm whether these results can be extrapolated to areas affected by surgery.

Step-by-step guide for a simplified model of porcine orthotopic liver transplant.

BACKGROUND: Based on similar anatomy, physiology, and size to humans, pigs provide an excellent means for studying new therapies related to orthotopic liver transplant (OLT). Techniques that have been described to date, however, are unnecessarily complex and increase the likelihood of morbidity and adverse outcome. MATERIALS AND METHODS: Male outbred weanling pigs underwent OLT according to our procedure, with a short anhepatic time (<20 min) and without veno-venous bypass or vasoactive substances during the anhepatic phase. Vascular anastomoses were performed identical to the clinical setting, and a simple stented choledochocholedochostomy was created. RESULTS: The authors have performed this procedure 130 times using four transplant models: standard, whole-liver (n = 10), small-for-size (n = 48), donor after cardiac death (n = 44), and donor adenoviral gene transfection (n = 28). The average cold ischemic and anhepatic times were 302 ± 43 and 17 ± 3 min, respectively. Hypotension was successfully treated with intravenous fluids. In all cases, the recipient survived the operation and was extubated. Survival to the end follow-up varied according to the model and was 56% (73/130) for all cases. At autopsy or euthanasia, no vascular thrombosis or outflow obstruction was found. Survival was 100% for pigs transplanted with standard, whole-liver grafts (n = 10). In this group, AST and bilirubin rose during the first 24 h after graft reperfusion, while the Quick prothrombin time (QPT) fell. By the fifth postoperative day, these parameters had returned to baseline. CONCLUSIONS: This model is straightforward and reproducible and offers surgeons and researchers the opportunity to perform OLT studies under clinically relevant conditions.

The influence of the explant technique on the hemodynamic profile during sequential domino liver transplantation in familial amyloid polyneuropathy patients.

Familial amyloidotic polyneuropathy (FAP) patients present adrenergic cardiac input blockade secondary to amyloid deposits and sympathetic neuropathy. Consequently, their capacity to compensate for hemodynamic changes is limited. To avoid hemodynamic disturbances in sequential liver transplants, a standard procedure with venovenous bypass or inferior vena cava preservation is contemplated. The aim of this study was to evaluate the impact of both techniques on the hemodynamic management and outcome of patients affected by FAP and scheduled for a domino liver transplantation program. We evaluated 36 FAP patients. Venovenous bypass was performed for 20 patients (the venovenous bypass group), whereas the vena cava preservation technique was used for the remaining 16 patients (the cava preservation group). The time that elapsed from FAP diagnosis to liver transplantation was 3.2 +/- 2.7 years. Peripheral neuropathy was present in all patients, autonomic dysfunction was present in 71%, and cardiac involvement was present in 69%. Renal and gastrointestinal manifestations were reported in 19% and 53% of patients, respectively. The 1-, 3-, and 5-year survival rates were 97%, 93%, and 93%, respectively. Intraoperative hemodynamic and cardiac disorders, need for vasoactive drugs, blood loss, and transfusion requirements were recorded. Postoperative outcome and cardiac and renal complications were also recorded. No significant differences in disease severity or demographic characteristics were observed. Among all the variables studied, only the total ischemia time and time in surgery were significantly longer in the venovenous bypass group patients (P < or = 0.05). During the postoperative period, the incidence of minor cardiovascular events, incidence of acute renal dysfunction, and outcomes were similar in the 2 groups. In conclusion, either preservation of the vena cava or the standard technique with venovenous bypass can be safely used in FAP patients during liver transplantation. Liver Transpl 15:869-875, 2009. (c) 2009 AASLD.