Max Guillot

Muscles susceptibility to ischemia-reperfusion injuries depends on fiber type specific antioxidant level

Muscle injury resulting from ischemia-reperfusion largely aggravates patient prognosis but whether and how muscle phenotype modulates ischemia-reperfusion-induced mitochondrial dysfunction remains to be investigated. We challenged the hypothesis that glycolytic muscles are more prone to ischemia-reperfusion-induced injury than oxidative skeletal muscles. We therefore determined simultaneously the effect of 3 h of ischemia induced by aortic clamping followed by 2 h of reperfusion (IR, n = 11) on both gastrocnemius and soleus muscles, as compared to control animals (C, n = 11). Further, we investigated whether tempol, an antioxidant mimicking superoxide dismutase, might compensate a reduced defense system, likely characterizing glycolytic muscles (IR-Tempol, n = 7). In the glycolytic gastrocnemius muscle, as compared to control, ischemia-reperfusion significantly decreased mitochondrial respiration (−30.28 ± 6.16%, p = 0.003), increased reactive oxygen species production (+79.15 ± 28.72%, p = 0.04), and decreased reduced glutathione (−28.19 ± 6.80%, p = 0.011). Less deleterious effects were observed in the oxidative soleus muscle (−6.44 ± 6.30%, +4.32 ± 16.84%, and −8.07 ± 10.84%, respectively), characterized by enhanced antioxidant defenses (0.63 ± 0.05 in gastrocnemius vs. 1.24 ± 0.08 μmol L−1 g−1 in soleus). Further, when previously treated with tempol, glycolytic muscle was largely protected against the deleterious effects of ischemia-reperfusion. Thus, oxidative skeletal muscles are more protected than glycolytic ones against ischemia-reperfusion, thanks to their antioxidant pool. Such pivotal data support that susceptibility to ischemia-reperfusion-induced injury differs between organs, depending on their metabolic phenotypes. This suggests a need to adapt therapeutic strategies to the specific antioxidant power of the target organ to be protected.

Cryopreservation with dimethyl sulfoxide prevents accurate analysis of skinned skeletal muscle fibers mitochondrial respiration

Impact of cryopreservation protocols on skeletal muscle mitochondrial respiration remains controversial. We showed that oxygen consumption with main mitochondrial substrates in rat skeletal muscles was higher in fresh samples than in cryopreserved samples and that this difference was not fixed but grow significantly with respiration rates with wide fluctuations around the mean difference. Very close results were observed whatever the muscle type and the substrate used. Importantly, the deleterious effects of ischemia-reperfusion observed on fresh samples vanished when cryopreserved samples were studied. These data demonstrate that this technic should probably be performed only extemporaneously.

An Uncommon Option for Surviving Bariatric Surgery: Regaining Weight!

In November 2011, a 32-year-old woman was admitted to the intensive care unit for acute respiratory failure. She had felt well consistently until February (including 2 pregnancies), when she underwent a noncomplicated sleeve gastrectomy for obesity (body mass index, 47 kg/m). Her weight gain, unrelated to any endocrine disease, had started with adolescence and was resistant to all attempts to lose weight. One month after bariatric surgery and a loss of 20 kg, she had a first episode of constant and diffuse abdominal pain with slightly increased plasma concentration of lipase, and pancreatitis was diagnosed. Recurrent monthly vomiting episodes occurred later with abdominal and leg pains unrelated to her menstrual cycle. To counter postoperative deficiencies, she was fully supplemented with all vitamins. She had been treated regularly with analgesic drugs in an attempt to relieve erratic pain. Three weeks before admission, leg pains intensified, and tetraparesis developed over 2 days. On admission (6 months after surgery), her body mass index was 21 kg/m and heart rate was 135 beats/min. She ad tetraparesis with diffuse allodynia and paresthesias, acial diplegia, and swallowing disorders with alveolar hyoventilation requiring mechanical ventilation. Laboratory test results showed hypokalemia (2.6 mmol/ ), hyponatremia (134 mmol/L), and moderately elevated iver enzymes (alanine aminotransferase 79 UI/L and aspartate minotransferase 47 UI/L) without cholestasis. Renal function, lood counts, hemostasis, and Lyme serology were normal, as ell as dosages of vitamins. Repeated cerebrospinal fluid exminations showed normal protein concentration without cells. lectromyography was compatible with severe motor axonal olyneuropathy. Magnetic resonance imaging showed focal ervical hyperintensity compatible with myelitis. Electroenephalography was normal. Supportive care was given, and immunoglobulins were nfused to treat a possible Guillain-Barre syndrome. No mprovement was noted during the first few days.

Liver transplantation in critically ill patients: Preoperative predictive factors of post-transplant mortality to avoid futility

The allocation of liver transplants to patients with acute liver failure (ALF) and acute‐on‐chronic liver failure (ACLF) with multi‐organ failure who are admitted in ICU remains controversial due to their high post‐transplant mortality rate and the absence of identified mortality risk factors.

Liver transplantation in case of acetaminophen poisoning: importance of assessment of the colon if arterial lactate increases despite appropriate care.

Assessment of the Colon if Arterial Lactate Increases Despite Appropriate Care Scarcity of organs justifies efficient transplantation decision making even in toxic acute liver failure (ALF). Modified King’s College Hospital criteria are widely accepted for decision making in emergency liver transplantation (LT) after acetaminophen poisoning: they have good specificity in identifying patients with poor prognosis, but are of low sensitivity in selecting patients who will die of ALF (1). Three of our recent clinical cases illustrate why the LT decision making process should also include careful and early digestive tract assessment. After deliberate acetaminophen poisoning, three young women with no previous medical history were referred for LT in the context of ALF with coma and lactate beyond 14 mmol/L (despite proper 24-hr fluid resuscitation). In these cases, the treatment with N-acetyl cysteine (NAC) had been started beyond 15 hr after acetaminophen intake. In the first patient, the LT proceeded without incident; 48 hr later, clinical worsening and absence of improvement attested in the biological liver tests (i.e., both aspartate aminotransferase and alanine aminotransferase increase and reincrease of arterial lactate) suggested primary liver dysfunction (Table 1). An emergency surgical reintervention disclosed diffuse patches of colon infarction without vascular obstruction, despite the fact that the colon had looked normal at the end of the first LT. Segmental resections were associated to total recovery. While on waiting list for 24 hr, the second patient unexpectedly developed stiffness of the leg with an increase in plasma creatine phosphokinase levels as already reported (2); subsequently, she was withdrawn from the LT list because liver tests no longer worsened. Despite full recovery of her liver tests, the patient developed long-lasting multiple organ failure related to focal colon lesions which resulted in shock requiring multiple segmental colon removal. She ultimately survived without LT. Histological lesions of the colon were similar to those reported previously (3): foci of necrosis and intramucosal hematoma were detected in the right colon. After careful rechecking of the abdominal CT scan taken at admission in connection with long-lasting arterial lactate increase, the presence of signs of mucosa ischemia and of hematoma was confirmed (Fig. 1). The third patient died with uncontrollable lactic academia while on waiting list for 4 days despite normal lactate on admission; the autopsy revealed macroscopic ischemic injury of the entire colon without thrombosis of conductance vessels. Our data further indicate that large doses of acetaminophen taken alone (i.e., without additional drugs or alcohol) trigger multiorgan insults after

Tracheotomy in the intensive care unit: guidelines from a French expert panel

Tracheotomy is widely used in intensive care units, albeit with great disparities between medical teams in terms of frequency and modality. Indications and techniques are, however, associated with variable levels of evidence based on inhomogeneous or even contradictory literature. Our aim was to conduct a systematic analysis of the published data in order to provide guidelines. We present herein recommendations for the use of tracheotomy in adult critically ill patients developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. These guidelines were conducted by a group of experts from the French Intensive Care Society (Société de Réanimation de Langue Française) and the French Society of Anesthesia and Intensive Care Medicine (Société Francaise d’Anesthésie Réanimation) with the participation of the French Emergency Medicine Association (Société Française de Médecine d’Urgence), the French Society of Otorhinolaryngology. Sixteen experts and two coordinators agreed to consider questions concerning tracheotomy and its practical implementation. Five topics were defined: indications and contraindications for tracheotomy in intensive care, tracheotomy techniques in intensive care, modalities of tracheotomy in intensive care, management of patients undergoing tracheotomy in intensive care, and decannulation in intensive care. The summary made by the experts and the application of GRADE methodology led to the drawing up of 8 formal guidelines, 10 recommendations, and 3 treatment protocols. Among the 8 formal guidelines, 2 have a high level of proof (Grade 1+/−) and 6 a low level of proof (Grade 2+/−). For the 10 recommendations, GRADE methodology was not applicable and instead 10 expert opinions were produced.