Protection of cerebral microcirculation, mitochondrial function and electrocortical activity by small-volume resuscitation with terlipressin in a model of haemorrhagic shock

Background During early treatment of haemorrhagic shock, cerebral perfusion pressure can be restored by small-volume resuscitation with vasopressors. Whether this therapy is improved with additional fluid remains unknown. We assessed the value of terlipressin and lactated Ringer’s solution (LR) on the early recovery of the microcirculation, tissue oxygenation, and mitochondrial and electrophysiological function in the rat cerebral cortex. Methods Animals treated with LR replacing three times (3x) the volume bled (n=26), terlipressin (n=27), terlipressin plus LR of 1x (n=26), 2x (n=16), or 3x (n=15) were compared with untreated (n=36) and sham-operated rats (n=17). In vivo confocal microscopy was used to assess cortical capillary perfusion, changes in tissue oxygen concentration, and mitochondrial membrane potential and redox state. Electrophysiological function was assessed by cortical somatosensory evoked potentials (SEPs), spinal cord dorsum potential, and peripheral electromyography. Results Compared with sham, the mean (SD) area of perfused vessels was lower in rats subjected to haemorrhagic shock: 82 (10)% vs. 38 (12)%; P<0.001) and impaired oxygen concentration, mitochondrial redox state (99±4 vs. 59±15 % of baseline; P<0.001), and SEPs (97±13% vs. 27±19% of baseline). Adminstration of terlipressin plus 1X or 2X LR was able to recover these measures, but terlipressin+3LR or 3LR alone were not as effective. Spinal cord dorsum potential was preserved in all groups, but no therapy protected electromyographic function. Conclusion Resuscitation from haemorrhagic shock using terlipressin with small-volume LR was superior to high-volume LR, with regard to cerebral microcirculation, and mitochondrial and electrophysiological function

Protection of cerebral microcirculation, mitochondrial function, and electrocortical activity by small-volume resuscitation with terlipressin in a rat model of haemorrhagic shock

BACKGROUND: During early treatment of haemorrhagic shock, cerebral perfusion pressure can be restored by small-volume resuscitation with vasopressors. Whether this therapy is improved with additional fluid remains unknown. We assessed the value of terlipressin and lactated Ringer's solution (LR) on early recovery of microcirculation, tissue oxygenation, and mitochondrial and electrophysiological function in the rat cerebral cortex. METHODS: Animals treated with LR replacing three times (3LR) the volume bled (n=26), terlipressin (n=27), terlipressin plus 1LR (n=26), 2LR (n=16), or 3LR (n=15) were compared with untreated (n=36) and sham-operated rats (n=17). In vivo confocal microscopy was used to assess cortical capillary perfusion, changes in tissue oxygen concentration, and mitochondrial membrane potential and redox state. Electrophysiological function was assessed by cortical somatosensory evoked potentials, spinal cord dorsum potential, and peripheral electromyography. RESULTS: Compared with sham treatment, haemorrhagic shock reduced the mean (SD) area of perfused vessels [82% (sd 10%) vs 38% (12%); P<0.001] and impaired oxygen concentration, mitochondrial redox state [99% (4%) vs 59% (15%) of baseline; P<0.001], and somatosensory evoked potentials [97% (13%) vs 27% (19%) of baseline]. Administration of terlipressin plus 1LR or 2LR was able to recover these measures, but terlipressin plus 3LR or 3LR alone were not as effective. Spinal cord dorsum potential was preserved in all groups, but no therapy protected electromyographic function. CONCLUSIONS: Resuscitation from haemorrhagic shock using terlipressin with small-volume LR was superior to high-volume LR, with regard to cerebral microcirculation, and mitochondrial and electrophysiological functions

TRANSPLANTE HEPÁTICO NA HEMOFILIA A GRAVE: MANEJO PERIOPERATÓRIO E RESULTADO PÓS-TRANSPLANTE

Introdução: O transplante hepático é um procedimento complexo, com alto risco de sangramento e necessidade significativa de transfusões, em pacientes com hemofilia o risco de complicações hemorrágicas e choque hipovolêmico são ainda mais elevados. Relatamos o caso de um paciente idoso que alcançou a cura da hemofilia A após transplante. Relato de caso: Paciente sexo masculino, 63 anos, diagnóstico de hemofilia A grave, cirrose hepática devido a HCV e carcinoma hepatocelular, MELD 29. Histórico de HAS, DM, DRC não dialítica e DAC. Uso profilático de concentrado de FVIII três vezes por semana. O paciente foi submetido a um transplante hepático de doador cadáver, explante difícil devido a múltiplas aderências intracavitárias. Implante do enxerto sem intercorrências, realizado utilizando-se a técnica de “Piggyback”para a reconstrução venosa, com boa reperfusão do órgão. Recebeu 4.000 UI de FVIII em bolus uma hora antes do procedimento e, durante a cirurgia, foram administrados uma unidade de concentrado de plaquetas por aférese e dois gramas de concentrado de fibrinogênio, guiadas pelo tromboelastograma. O paciente apresentou síndrome de reperfusão, necessitando de drogas vasoativas em altas doses para manter a pressão arterial. Após o procedimento, desenvolveu acidose lática refratária e oligúria, sendo necessário iniciar hemodiálise contínua devido à lesão renal aguda. A imunossupressão inicial com tacrolimus foi substituída por micofenolato devido a alterações na função renal. O paciente permaneceu na UTI por cinco dias, com boa evolução clínica e laboratorial. A profilaxia foi conduzida conforme as diretrizes do Manual de Hemofilia do Ministério da Saúde: 4.000 UI de FVIII uma hora antes da cirurgia, 2.000 UI de FVIII a cada 12 horas do 1ºao 7ºpós-operatório, e 2.000 UI de FVIII uma vez ao dia do 8ºao 14ºpós-operatório. No entanto, devido à boa evolução do paciente e níveis de FVIII superiores a 20% já no 2ºpós-operatório, a profilaxia foi suspensa no 3ºpós-operatório, não sendo necessárias novas reposições. Recebeu ainda duas unidades de Concentrado de Hemácias durante a internação, devido queda da hemoglobina no pós operatorio. O paciente recebeu alta hospitalar 20 dias após o transplante hepático. Discussão: A infecção por HCV é a principal causa de doença hepática em pacientes com hemofilia. Durante a década de 1970, a maioria dos pacientes com hemofilia foi infectada pelo HCV devido à transfusão de hemoderivados e concentrados de fatores de coagulação. Considerando a idade e o diagnóstico do paciente, é possível que ele tenha sido infectado pelo HCV devido às transfusões que recebeu no passado. Apesar dos desafios hemostáticos associados ao transplante nesta população, os resultados para candidatos hemofílicos não são inferiores aos de pacientes não hemofílicos. Avanços no manejo perioperatório, nas técnicas cirúrgicas e na preservação do enxerto contribuíram para uma redução significativa nas transfusões nas últimas décadas. No caso descrito, o paciente teve baixa demanda transfusional e sangramento dentro do esperado durante o procedimento. As complicações pós-cirúrgicas, embora graves, foram resolvidas em poucos dias. O caso apresentado mostra uma resolução imediata dos níveis de fator VIII e uma evolução favorável da saúde do paciente nos anos subsequentes, com normalização dos níveis de fator VIII, sugerindo que o transplante hepático pode ser uma alternativa terapêutica eficaz para pacientes com hemofilia A

Vasopressin analog terlipressin attenuates kidney injury in hemorrhagic shock

Background In hemorrhagic shock (HS), volume replacement with crystalloid solution can restore the hemodynamic status and decrease mortality. However, it can also lead to tissue edema and pulmonary congestion, as well as increasing vascular permeability. Here, we analyzed the effects that resuscitation with lactated Ringer's solution (LRS) or administration of the vasopressin analog terlipressin has on renal function in a porcine model of HS. Methods Using pressure-controlled bleeding, we induced pigs to HS, maintaining mean arterial pressure (MAP) at 40 mm Hg for 30 min. Animals were divided into 4 groups: sham (anesthesia only); shock-only (HS induction); shock+LRS (HS induction and subsequent resuscitation with LRS at 3 times the volume of blood removed); and shock+Terli (HS induction and subsequent bolus administration of 2 mg of terlipressin). Parameters were evaluated at baseline, then at 30, 60, and 120 min after treatment (T30, T60, and T120, respectively). Animals were euthanized at T60 or T120. Results Both treatments restored MAP to baseline values. At T30 and T60, creatinine clearance was highest in shock+LRS pigs, whereas it was highest in shock+Terli pigs at T120. Both treatments initially induced hyponatremia, although urinary excretion of all ions was higher in shock+LRS pigs at T30. Both treatments restored Na–K–2Cl cotransporter expression, whereas only terlipressin restored aquaporin 2 expression. Both treatments also prevented HS-induced acute tubular necrosis. Expression of the vasopressin receptors V1a and V2 was highest in shock-only pigs. At T120, V1a expression was lowest in shock+LRS pigs. Discussion Terlipressin might be useful for preventing HS-induced acute kidney injury

Perioperative goal-directed therapy: what's the best study design to investigate its impact on patient outcome?

SCOPUS: ed.jDecretOANoAutActifinfo:eu-repo/semantics/publishe