Consenso Colombiano para la prevención, diagnóstico y manejo de condiciones trombóticas en pacientes adultos con COVID-19: aplicando el Marco de la Evidencia a la Decisión (EtD) GRADE / Colombian consensus for the prevention, diagnosis and treatment of thrombotic conditions in adult patients with COVID-19: applying GRADE Evidence to Decision (EtD) Frameworks

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Abstract Recent studies have reported the occurrence of thrombotic phenomena or coagulopathy in patients with COVID-19. There are divergent positions regarding the prevention, diagnosis, and treatment of these phenomena, and current clinical practice is based solely on deductions by extension from retrospective studies, case series, observational studies, and international guidelines developed prior to the pandemic. In this context, the aim was to generate a group of recommendations on the prevention, diagnosis and management of thrombotic complications associated with COVID-19. Methods: A rapid guidance was carried out applying the GRADE Evidence to Decision (EtD) frameworks and an iterative participation system, with statistical and qualitative analysis. Results: 31 clinical recommendations were generated focused on: a) Coagulation tests in symptomatic adults with suspected infection or confirmed SARS CoV-2 infection; b) Thromboprophylaxis in adults diagnosed with COVID-19 (Risk scales, thromboprophylaxis for outpatient, in-hospital management, and duration of thromboprophylaxis after discharge from hospitalization), c) Diagnosis and treatment of thrombotic complications, and d) Management of people with previous indication of anticoagulant agents. Conclusions: Recommendations of this consensus guide clinical decision-making regarding the prevention, diagnosis, and treatment of thrombotic phenomena in patients with COVID-19, and represent an agreement that will help decrease the dispersion in clinical practices according to the challenge imposed by the pandemic.

Interventions for preventing high altitude illness: Part 3. Miscellaneous and non-pharmacological interventions.

BACKGROUND: High altitude illness (HAI) is a term used to describe a group of mainly cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (˜ 8200 feet). Acute mountain sickness (AMS), high altitude cerebral oedema (HACE), and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude ascent. In this, the third of a series of three reviews about preventive strategies for HAI, we assessed the effectiveness of miscellaneous and non-pharmacological interventions. OBJECTIVES: To assess the clinical effectiveness and adverse events of miscellaneous and non-pharmacological interventions for preventing acute HAI in people who are at risk of developing high altitude illness in any setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) in January 2019. We adapted the MEDLINE strategy for searching the other databases. We used a combination of thesaurus-based and free-text search terms. We scanned the reference lists and citations of included trials and any relevant systematic reviews that we identified for further references to additional trials. SELECTION CRITERIA: We included randomized controlled trials conducted in any setting where non-pharmacological and miscellaneous interventions were employed to prevent acute HAI, including preacclimatization measures and the administration of non-pharmacological supplements. We included trials involving participants who are at risk of developing high altitude illness (AMS or HACE, or HAPE, or both). We included participants with, and without, a history of high altitude illness. We applied no age or gender restrictions. We included trials where the relevant intervention was administered before the beginning of ascent. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures employed by Cochrane. MAIN RESULTS: We included 20 studies (1406 participants, 21 references) in this review. Thirty studies (14 ongoing, and 16 pending classification (awaiting)) will be considered in future versions of this suite of three reviews as appropriate. We report the results for the primary outcome of this review (risk of AMS) by each group of assessed interventions.Group 1. Preacclimatization and other measures based on pressureUse of simulated altitude or remote ischaemic preconditioning (RIPC) might not improve the risk of AMS on subsequent exposure to altitude, but this effect is uncertain (simulated altitude: risk ratio (RR) 1.18, 95% confidence interval (CI) 0.82 to 1.71; I² = 0%; 3 trials, 140 participants; low-quality evidence. RIPC: RR 3.0, 95% CI 0.69 to 13.12; 1 trial, 40 participants; low-quality evidence). We found evidence of improvement of this risk using positive end-expiratory pressure (PEEP), but this information was derived from a cross-over trial with a limited number of participants (OR 3.67, 95% CI 1.38 to 9.76; 1 trial, 8 participants; low-quality evidence). We found scarcity of evidence about the risk of adverse events for these interventions.Group 2. Supplements and vitaminsSupplementation of antioxidants, medroxyprogesterone, iron or Rhodiola crenulata might not improve the risk of AMS on exposure to high altitude, but this effect is uncertain (antioxidants: RR 0.58, 95% CI 0.32 to 1.03; 1 trial, 18 participants; low-quality evidence. Medroxyprogesterone: RR 0.71, 95% CI 0.48 to 1.05; I² = 0%; 2 trials, 32 participants; low-quality evidence. Iron: RR 0.65, 95% CI 0.38 to 1.11; I² = 0%; 2 trials, 65 participants; low-quality evidence. R crenulata: RR 1.00, 95% CI 0.78 to 1.29; 1 trial, 125 participants; low-quality evidence). We found evidence of improvement of this risk with the administration of erythropoietin, but this information was extracted from a trial with issues related to risk of bias and imprecision (RR 0.41, 95% CI 0.20 to 0.84; 1 trial, 39 participants; very low-quality evidence). Regarding administration of ginkgo biloba, we did not perform a pooled estimation of RR for AMS due to considerable heterogeneity between the included studies (I² = 65%). RR estimates from the individual studies were conflicting (from 0.05 to 1.03; low-quality evidence). We found scarcity of evidence about the risk of adverse events for these interventions.Group 3. Other comparisonsWe found heterogeneous evidence regarding the risk of AMS when ginkgo biloba was compared with acetazolamide (I² = 63%). RR estimates from the individual studies were conflicting (estimations from 0.11 (95% CI 0.01 to 1.86) to 2.97 (95% CI 1.70 to 5.21); low-quality evidence). We found evidence of improvement when ginkgo biloba was administered along with acetazolamide, but this information was derived from a single trial with issues associated to risk of bias (compared to ginkgo biloba alone: RR 0.43, 95% CI 0.26 to 0.71; 1 trial, 311 participants; low-quality evidence). Administration of medroxyprogesterone plus acetazolamide did not improve the risk of AMS when compared to administration of medroxyprogesterone or acetazolamide alone (RR 1.33, 95% CI 0.50 to 3.55; 1 trial, 12 participants; low-quality evidence). We found scarcity of evidence about the risk of adverse events for these interventions. AUTHORS' CONCLUSIONS: This Cochrane Review is the final in a series of three providing relevant information to clinicians, and other interested parties, on how to prevent high altitude illness. The assessment of non-pharmacological and miscellaneous interventions suggests that there is heterogeneous and even contradictory evidence related to the effectiveness of these prophylactic strategies. Safety of these interventions remains as an unclear issue due to lack of assessment. Overall, the evidence is limited due to its quality (low to very low), the relative paucity of that evidence and the number of studies pending classification for the three reviews belonging to this series (30 studies either awaiting classification or ongoing). Additional studies, especially those comparing with pharmacological alternatives (such as acetazolamide) are required, in order to establish or refute the strategies evaluated in this review.

Interventions for preventing high altitude illness: Part 2. Less commonly-used drugs.

BACKGROUND: High altitude illness (HAI) is a term used to describe a group of mainly cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (˜ 8200 feet). Acute mountain sickness (AMS), high altitude cerebral oedema (HACE) and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude ascent. In this second review, in a series of three about preventive strategies for HAI, we assessed the effectiveness of five of the less commonly used classes of pharmacological interventions. OBJECTIVES: To assess the clinical effectiveness and adverse events of five of the less commonly used pharmacological interventions for preventing acute HAI in participants who are at risk of developing high altitude illness in any setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) in May 2017. We adapted the MEDLINE strategy for searching the other databases. We used a combination of thesaurus-based and free-text search terms. We scanned the reference lists and citations of included trials and any relevant systematic reviews that we identified for further references to additional trials. SELECTION CRITERIA: We included randomized controlled trials conducted in any setting where one of five classes of drugs was employed to prevent acute HAI: selective 5-hydroxytryptamine(1) receptor agonists; N-methyl-D-aspartate (NMDA) antagonist; endothelin-1 antagonist; anticonvulsant drugs; and spironolactone. We included trials involving participants who are at risk of developing high altitude illness (AMS or HACE, or HAPE, or both). We included participants with and without a history of high altitude illness. We applied no age or gender restrictions. We included trials where the relevant medication was administered before the beginning of ascent. We excluded trials using these drugs during ascent or after ascent. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures employed by Cochrane. MAIN RESULTS: We included eight studies (334 participants, 9 references) in this review. Twelve studies are ongoing and will be considered in future versions of this review as appropriate. We have been unable to obtain full-text versions of a further 12 studies and have designated them as 'awaiting classification'. Four studies were at a low risk of bias for randomization; two at a low risk of bias for allocation concealment. Four studies were at a low risk of bias for blinding of participants and personnel. We considered three studies at a low risk of bias for blinding of outcome assessors. We considered most studies at a high risk of selective reporting bias.We report results for the following four main comparisons.Sumatriptan versus placebo (1 parallel study; 102 participants)Data on sumatriptan showed a reduction of the risk of AMS when compared with a placebo (risk ratio (RR) = 0.43, CI 95% 0.21 to 0.84; 1 study, 102 participants; low quality of evidence). The one included study did not report events of HAPE, HACE or adverse events related to administrations of sumatriptan.Magnesium citrate versus placebo (1 parallel study; 70 participants)The estimated RR for AMS, comparing magnesium citrate tablets versus placebo, was 1.09 (95% CI 0.55 to 2.13; 1 study; 70 participants; low quality of evidence). In addition, the estimated RR for loose stools was 3.25 (95% CI 1.17 to 8.99; 1 study; 70 participants; low quality of evidence). The one included study did not report events of HAPE or HACE.Spironolactone versus placebo (2 parallel studies; 205 participants)Pooled estimation of RR for AMS was not performed due to considerable heterogeneity between the included studies (I² = 72%). RR from individual studies was 0.40 (95% CI 0.12 to 1.31) and 1.44 (95% CI 0.79 to 2.01; very low quality of evidence). No events of HAPE or HACE were reported. Adverse events were not evaluated.Acetazolamide versus spironolactone (1 parallel study; 232 participants)Data on acetazolamide compared with spironolactone showed a reduction of the risk of AMS with the administration of acetazolamide (RR = 0.36, 95% CI 0.18 to 0.70; 232 participants; low quality of evidence). No events of HAPE or HACE were reported. Adverse events were not evaluated. AUTHORS' CONCLUSIONS: This Cochrane Review is the second in a series of three providing relevant information to clinicians and other interested parties on how to prevent high altitude illness. The assessment of five of the less commonly used classes of drugs suggests that there is a scarcity of evidence related to these interventions. Clinical benefits and harms related to potential interventions such as sumatriptan are still unclear. Overall, the evidence is limited due to the low number of studies identified (for most of the comparison only one study was identified); limitations in the quality of the evidence (moderate to low); and the number of studies pending classification (24 studies awaiting classification or ongoing). We lack the large and methodologically sound studies required to establish or refute the efficacy and safety of most of the pharmacological agents evaluated in this review.

Interventions for preventing high altitude illness: Part 1. Commonly-used classes of drugs.

BACKGROUND: High altitude illness (HAI) is a term used to describe a group of cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (8202 feet). Acute hypoxia, acute mountain sickness (AMS), high altitude cerebral oedema (HACE) and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude. In this review, the first in a series of three about preventive strategies for HAI, we assess the effectiveness of six of the most recommended classes of pharmacological interventions. OBJECTIVES: To assess the clinical effectiveness and adverse events of commonly-used pharmacological interventions for preventing acute HAI. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), Embase (OVID), LILACS and trial registries in January 2017. We adapted the MEDLINE strategy for searching the other databases. We used a combination of thesaurus-based and free-text terms to search. SELECTION CRITERIA: We included randomized-controlled and cross-over trials conducted in any setting where commonly-used classes of drugs were used to prevent acute HAI. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included 64 studies (78 references) and 4547 participants in this review, and classified 12 additional studies as ongoing. A further 12 studies await classification, as we were unable to obtain the full texts. Most of the studies were conducted in high altitude mountain areas, while the rest used low pressure (hypobaric) chambers to simulate altitude exposure. Twenty-four trials provided the intervention between three and five days prior to the ascent, and 23 trials, between one and two days beforehand. Most of the included studies reached a final altitude of between 4001 and 5000 metres above sea level. Risks of bias were unclear for several domains, and a considerable number of studies did not report adverse events of the evaluated interventions. We found 26 comparisons, 15 of them comparing commonly-used drugs versus placebo. We report results for the three most important comparisons: Acetazolamide versus placebo (28 parallel studies; 2345 participants)The risk of AMS was reduced with acetazolamide (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.39 to 0.56; I2 = 0%; 16 studies; 2301 participants; moderate quality of evidence). No events of HAPE were reported and only one event of HACE (RR 0.32, 95% CI 0.01 to 7.48; 6 parallel studies; 1126 participants; moderate quality of evidence). Few studies reported side effects for this comparison, and they showed an increase in the risk of paraesthesia with the intake of acetazolamide (RR 5.53, 95% CI 2.81 to 10.88, I2 = 60%; 5 studies, 789 participants; low quality of evidence). Budenoside versus placebo (2 parallel studies; 132 participants)Data on budenoside showed a reduction in the incidence of AMS compared with placebo (RR 0.37, 95% CI 0.23 to 0.61; I2 = 0%; 2 studies, 132 participants; low quality of evidence). Studies included did not report events of HAPE or HACE, and they did not find side effects (low quality of evidence). Dexamethasone versus placebo (7 parallel studies; 205 participants)For dexamethasone, the data did not show benefits at any dosage (RR 0.60, 95% CI 0.36 to 1.00; I2 = 39%; 4 trials, 176 participants; low quality of evidence). Included studies did not report events of HAPE or HACE, and we rated the evidence about adverse events as of very low quality. AUTHORS' CONCLUSIONS: Our assessment of the most commonly-used pharmacological interventions suggests that acetazolamide is an effective pharmacological agent to prevent acute HAI in dosages of 250 to 750 mg/day. This information is based on evidence of moderate quality. Acetazolamide is associated with an increased risk of paraesthesia, although there are few reports about other adverse events from the available evidence. The clinical benefits and harms of other pharmacological interventions such as ibuprofen, budenoside and dexamethasone are unclear. Large multicentre studies are needed for most of the pharmacological agents evaluated in this review, to evaluate their effectiveness and safety.

Validación transcultural y lingüística de la escala de sedación y agitación Richmond al español / Transcultural and linguistic adaptation of the Richmond Agitation-Sedation Scale to Spanish

Introduction: Goal oriented sedation is standard in the management of critically ill patients, but its systematic evaluation is not frequent. The Richmond agitation sedation scale's efficient operative features make it a validated instrument for sedation assessment. Objectives: To translate and validate the Richmond agitation sedation scale into Spanish. Method: A cultural and linguistic adaptation study was designed. Translation into Spanish included back-translation and pilot testing. The inter-rater reliability testing was conducted in Clínica Colombia's cardiovascular and general intensive care unit, including 100 patients mechanically ventilated and sedated. Inter-rater reliability was tested using Kappa statistics and Intra-class correlation coefficient. This study was approved by Fundación Universitaria Sanitas Research and Ethics Institute and Clínica Sanitas Research Committee. Results: 300 assessments using the Spanish version of the Richmond agitation sedation scale were performed by three independent evaluators. The intra-class correlation coefficient was 0.977 (CI 95% 0.968-0.984). The kappa was 0.84 between the first and second evaluators 0.85 between the first and third evaluators and 0.86 between the second and third evaluators. Conclusion: The product of this study, the Spanish version of the Richmond agitation sedation scale, is conceptually equivalent to the original scale, being reproducible and understandable to physicians whose native language is Spanish.

Introducción: La sedación por metas es un estándar en el manejo del paciente crítico pero su evaluación sistemática no es frecuente, la escala de sedación y agitación Richmond es un instrumento con características operativas eficientes para evaluar sedación. Objetivo: Traducir y validar la escala de sedación y agitación Richmond al idioma español. Método: Se diseñó un estudio de adaptación transcultural y lingüística y validación de instrumento. La traducción al idioma español incluyó una traducción reversa y una prueba piloto. Las evaluaciones para la validación se realizaron con 100 pacientes bajo sedación, ventilados mecánicamente en dos unidades de cuidados intensivos, una polivalente y otra cardiovascular de la Clínica Universitaria Colombia. La fiabilidad entre los observadores fue probada utilizando el estadístico kappa y el coeficiente de correlación intraclase. El estudio contó con la aprobación del instituto de investigaciones y comité de ética de la Fundación Universitaria Sanitas y comité de investigaciones de Clínica Sanitas. Resultados: Se realizaron evaluaciones secuenciales e independientes por tres entrevistadores, completando 300 valoraciones con la traducción de la escala en español. El coeficiente de correlación intraclase fue de 0,977 (IC 95% 0,968 - 0,984). La concordancia cualitativa entre los evaluadores también fue alta con un kappa de 0,84 entre el primer y segundo evaluador, 0,85 entre el primer y tercer evaluador y 0,86 entre el segundo y tercero. Conclusión: La versión en español de la escala de sedación y agitación Richmond producto de este estudio, resulta conceptualmente equivalente a la original, es reproducible y comprensible para médicos de habla hispana.

Reversion of Severe Mitral Insufficiency in Peripartum Cardiomyopathy Using Levosimendan.

Idiopathic peripartum cardiomyopathy presenting with heart failure is a true diagnostic and treatment challenge. Goal oriented clinical management aims at the relapse of left ventricular systolic dysfunction. A 35-year-old patient on her 12th day post-delivery presents progressive signs of heart failure. Transthoracic echocardiography showed severe mitral insufficiency, mild left ventricular dysfunction, mild tricuspid insufficiency, severe pulmonary hypertension, and right atrial enlargement. With wet and cold heart failure signs, the patient was a candidate for inodilator cardiovascular support and volume depletion therapy. As the patient presented a persistent tachycardia at rest, levosimendan was chosen over dobutamine. Levosimendan was administered at a dose of 0.2 µg/kg/min during a period of 24 hours. After inodilator therapy, the patient's signs and symptoms of heart failure began to decrease, showing improvement of dyspnea, mitral murmur grade went from IV/IV to II/IV, filling pressures and systemic and pulmonary resistance indexes decreased, arterial blood gases improved, and an echocardiography performed 72 h later showed non-dilated cardiomyopathy, mild cardiac contractile dysfunction, mild mitral insufficiency, type I diastolic dysfunction and improvement of pulmonary hypertension. Cardiovascular function in peripartum cardiomyopathy tends to go back to normality in 23-41% of the cases, but in a large group of patients, severe ventricle dysfunction remains months after initial symptoms. This article describes the diagnostic process of a patient with peripartum cardiomyopathy and a successful reversion of a severe case of mitral insufficiency using levosimendan as a new therapeutic strategy in this clinical context.

Hipotermia terapéutica posreanimación cardiopulmonar en el posparto inmediato de una paciente atendida en el Hospital de San José, en Bogotá (Colombia) en 2013: reporte de un caso y revisión de la literatura / Post-cardiopulmonary resuscitation therapeutic hypothermia during the immediate post-partum period in a patient seen at San Jose Hospital in Bogota in 2013: Case Report and review of the literature

Objetivo: reportar el caso de una paciente que presentó paro cardiaco en su posparto inmediato, la cual fue manejada con hipotermia terapéutica posreanimación con resultados neurológicos favorables, y realizar una revisión de la literatura publicada acerca de hipotermia posreanimación en el embarazo.Materiales y métodos: se presenta el caso de una paciente con embarazo de 37 semanas, quien es remitida por preeclampsia severa a una institución privada de cuarto nivel de complejidad ubicada en Bogotá (Colombia). La paciente es llevada a cesárea, y en el alumbramiento desarrolla eclampsia, con deterioro respiratorio, hipoxemia y bradicardia que progresa a ritmo de paro en asistolia, con recuperación del ritmo sinusal luego de 15 minutos de reanimación cardiopulmonar (RCP), pero con criterios para un estado de coma residual. Se establece entonces un protocolo de neuroprotección con hipotermia sostenida a 33 grados durante 24 horas y posterior recalentamiento gradual. El desenlace final fue favorable, con recuperación del estado de conciencia y mínimas secuelas motoras.Para la revisión del tema se realizó una búsqueda en las bases de datos de la literatura especializadas en medicina (Medline vía PubMed, Embase) con los términos MESH: "hipotermia terapéutica", "embarazo", "paro cardiaco", sin restricción de idioma o de tiempo.Resultados: en PubMed se encontraron cuatro estudios con los criterios de búsqueda, y en Embase siete se referían al tema, los cuales incluían los cuatro reportes de casos ya encontrados en PubMed, dos reportes de casos adicionales y una revisión de paro cardiaco materno que discute en sus apartes el tema de hipotermia terapéutica en esta población. En la revisión de referencias bibliográficas se identificó una guía de práctica clínica y un artículo de revisión. Conclusiones: en la literatura publicada se describe la hipotermia terapéutica como una terapia benéfica para la paciente gestante, que podría ser considerada como parte de los cuidados posparo cardiaco como medida de protección neurológica. Se requieren estudios que incorporen mayor número de pacientes, y estudios controlados que evalúen la efectividad y seguridad de la técnica para la madre y el feto.

Objective: To report the case of a patient who went into cardiac arrest in the immediate post-partum period and was managed with post-resuscitation therapeutic hy pothermia with a favourable neurologic outcome; and to conduct a review of the published literature on post-resuscitation hypothermia in pregnancy.Materials and methods: We present the case of a patient in her 37th week of gestation, referred because of severe pre-eclampsia to a private, level IV institution in Bogotá, Colombia. The patient underwent cesarean section and during childbirth she developed eclampsia with respiratory distress, hypoxemia and bradycardia that progressed to cardiac arrest in asystole. Sinus rhythm returned after 15 minutes of cardiopulmonary resuscitation (CPR) but the patient was in a status consistent with residual coma. A neuroprotection protocol was initiated with hypothermia, maintained at 33 degrees over a 24- hour period, and then followed by gradual warming. The final outcome was favourable, with recovery of consciousness and negligible motor sequelae.For the review of the literature, a search was conducted in Medline via the PubMed and Embase databases using MESH terms for the key words therapeutic hypothermia, pregnancy, cardiac arrest, with no restriction of language or time.Results: Overall, 4 studies that met the search criteria were found in PubMed. In Embase, 7 referred to the topic, including the 4 case reports already found in PubMed plus two additional case reports and a review of maternal cardiac arrest that discusses therapeutic hypothermia in this population. The review of the bibliographic references resulted in the identification of a clinical practice guideline and one additional review article. Conclusions: Therapeutic hy pothermia is described in the published literature as a beneficial therapy that could be considered part of post- cardiac arrest care as a measure of neurological protection in the pregnant patient. Studies with larger numbers of patients and controlled trials to assess the effectiveness and safety of the technique for the mother and the foetus are needed.