Vincent Piriou

Desflurane-induced preconditioning alters calcium-induced mitochondrial permeability transition.

BackgroundRecent investigations have focused on the pivotal role of the mitochondria in the underlying mechanisms volatile anesthetic-induced myocardial preconditioning. This study aimed at examining the effect of anesthetic preconditioning on mitochondrial permeability transition (MPT) pore opening. MethodsAnesthetized open chest rabbits were randomized to one of four groups and underwent 10 min of ischemia, except for the sham 1 group (n = 12). Before this, they underwent a treatment period consisting of (1) no intervention (ischemic group; n = 12), (2) 30 min of desflurane inhalation (8.9% end-tidal concentration) followed by a 15-min washout period (desflurane group; n = 12), or (3) ischemic preconditioning (IPC group; n = 12). A second set of experiments was performed to evaluate the effect of a putative mitochondrial adenosine triphosphate–sensitive potassium channel antagonist, 5-hydroxydecanoate (5-HD). The animals underwent the same protocol as previously, plus pretreatment with 5 mg/kg 5-HD. They were randomized to one of five groups: the sham 2 group, receiving no 5-HD (n = 12); the sham 5-HD group (n = 12); the ischemic 5-HD group (n = 12), the desflurane 5-HD group (n = 12), and the IPC 5-HD group (n = 12). At the end of the protocol, the hearts were excised, and mitochondria were isolated. MPT pore opening was assessed by measuring the amount of calcium required to trigger a massive calcium release indicative of MPT pore opening. ResultsDesflurane and IPC group mitochondria needed a higher calcium load than ischemic group mitochondria (362 ± 84, 372 ± 74, and 268 ± 110 &;m calcium, respectively; P < 0.05) to induce MPT pore opening. The sham 1 and sham 2 groups needed a similar amount of calcium to trigger mitochondrial calcium release (472 ± 70 and 458 ± 90 &mgr;m calcium, respectively). 5-HD preadministration had no effect on sham animals (458 ± 90 and 440 ± 128 &mgr;m calcium without and with 5-HD, respectively) and ischemic group animals (268 ± 110 and 292 ± 102 &mgr;m calcium without and with 5-HD, respectively) but abolished the effects of desflurane on calcium-induced MPT pore opening (362 ± 84 &mgr;m calcium without 5-HD vs. 238 ± 96 &mgr;m calcium with 5-HD; P < 0.05) and IPC (372 ± 74 &mgr;m calcium without 5-HD vs. 270 ± 104 &mgr;m calcium with 5-HD; P < 0.05). ConclusionLike ischemic preconditioning, desflurane improved the resistance of the transition pore to calcium-induced opening. This effect was inhibited by 5-HD, suggesting a link between mitochondrial adenosine triphosphate–sensitive potassium and MPT.

Prevention of isoflurane-induced preconditioning by 5-hydroxydecanoate and gadolinium: possible involvement of mitochondrial adenosine triphosphate-sensitive potassium and stretch-activated channels.

BACKGROUND Both mitochondrial adenosine triphosphate-sensitive potassium (MKATP) channels (selectively blocked by 5-hydroxydecanoate) and stretch-activated channels (blocked by gadolinium) have been involved in the mechanism of ischemic preconditioning. Isoflurane can reproduce the protection afforded by ischemic preconditioning. We sought to determine whether isoflurane-induced preconditioning may involve MKATP and stretch-activated channels. METHODS Anesthetized open-chest rabbits underwent 30 min of coronary occlusion followed by 3 h of reperfusion. Before this, rabbits were randomized into one of six groups and underwent a treatment period consisting of either no intervention for 40 min (control group; n = 9) or 15 min of isoflurane inhalation (1.1% end tidal) followed by a 15-min washout period (isoflurane group; n = 9). The two groups received an intravenous bolus dose of either 5-hydroxydecanoate (5 mg/kg) or gadolinium (40 micromol/kg) before coronary occlusion and reperfusion (5-hydroxydecanoate, n = 9; gadolinium, n = 7). Two additional groups received 5-hydroxydecanoate or gadolinium before isoflurane exposure (isoflurane-5-hydroxydecanoate, n = 10; isoflurane-gadolinium, n = 8). Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining. RESULTS Area at risk was comparable among the six groups (29 +/- 7, 30 +/- 5, 27 +/- 6, 35 +/- 7, 31 +/- 7, and 27 +/- 4% of the left ventricle in the control, isoflurane, isoflurane-5-hydroxydecanoate, 5-hydroxydecanoate, isoflurane-gadolinium, and gadolinium groups, respectively). Infarct size averaged 60 +/- 20% (SD) in untreated controls versus 54 +/- 27 and 65 +/- 15% of the risk zone in 5-hydroxydecanoate- and gadolinium-treated controls (P = nonsignificant). In contrast, infarct size in the isoflurane group was significantly reduced to 26 +/- 11% of the risk zone (P < 0.05 vs.control). Both 5-hydroxydecanoate and gadolinium prevented this attenuation: infarct size averaged 68 +/- 23 and 56 +/- 21% of risk zone in the isoflurane-5-hydroxydecanoate and isoflurane-gadolinium groups, respectively (P = nonsignificant vs.control). CONCLUSION 5-Hydroxydecanoate and gadolinium inhibited pharmacologic preconditioning by isoflurane. This result suggests that MKATP channels and mechanogated channels are probably involved in this protective mechanism.

Non-cardiac surgery in patients with coronary stents: the RECO study

Context Interruption or maintenance of oral antiplatelet therapy (OAT) during an invasive procedure may result in ischaemic and/or haemorrhagic complications. There is currently a lack of clear guidance regarding the issue of treatment interruption during surgical procedures. Objective To evaluate the rate of major adverse cardiac and cerebrovascular events (MACCEs) and major or minor bleeding complications and their associated independent correlates in coronary stented patients undergoing urgent or planned non-cardiac surgery. Design, setting, and patients Prospective, multicentre, observational cohort study of 1134 consecutive patients with coronary stents. Main outcome measures The co-primary endpoints consisted of the incidence of MACCE and major bleeding within the first 30 days of an invasive procedure. Results MACCE and haemorrhagic complications were observed in 124 (10.9%) and 108 (9.5%) patients, respectively, within an average time delay from invasive procedure to event of 3.3±3.9 and 5.3±5.3 days. Independent preoperative correlates for MACCE were complete OAT interruption for more than 5 days prior to surgery, preoperative haemoglobin <10 g/dl, creatinine clearance of <30 ml/min and emergency or high-risk surgery. Independent factors for haemorrhagic complications were preoperative haemoglobin <10 g/dl, creatinine clearance between 30 and 60 ml/min, a delay from stent implantation to surgery <3 months and high-risk surgery according to the Lee classification. Conclusions Patients with coronary stents undergoing an invasive procedure are at high risk of perioperative myocardial infarction including stent thrombosis irrespective of the stent type and major bleeding. Interruption of OAT more than 5 days prior to an invasive procedure is a key player for MACCE. Clinical Trial Registration NCT01045850.

Pulse pressure variation and stroke volume variation during increased intra-abdominal pressure: an experimental study

IntroductionThe aim of this study was to evaluate dynamic indices of fluid responsiveness in a model of intra-abdominal hypertension.MethodsNine mechanically-ventilated pigs underwent increased intra-abdominal pressure (IAP) by abdominal banding up to 30 mmHg and then fluid loading (FL) at this IAP. The same protocol was carried out in the same animals made hypovolemic by blood withdrawal. In both volemic conditions, dynamic indices of preload dependence were measured at baseline IAP, at 30 mmHg of IAP, and after FL. Dynamic indices involved respiratory variations in stroke volume (SVV), pulse pressure (PPV), and systolic pressure (SPV, %SPV and Δdown). Stroke volume (SV) was measured using an ultrasound transit-time flow probe placed around the aortic root. Pigs were considered to be fluid responders if their SV increased by 15% or more with FL. Indices of fluid responsiveness were compared with a Mann-Whitney U test. Then, receiver operating characteristic (ROC) curves were generated for these parameters, allowing determination of the cut-off values by using Youdens method.ResultsFive animals before blood withdrawal and all animals after blood withdrawal were fluid responders. Before FL, SVV (78 ± 19 vs 42 ± 17%), PPV (64 ± 18 vs 37 ± 15%), SPV (24 ± 5 vs 18 ± 3 mmHg), %SPV (24 ± 4 vs 17 ± 3%) and Δdown (13 ± 5 vs 6 ± 4 mmHg) were higher in responders than in non-responders (P < 0.05). Areas under ROC curves were 0.93 (95% confidence interval: 0.80 to 1.06), 0.89 (0.70 to 1.07), 0.90 (0.74 to 1.05), 0.92 (0.78 to 1.06), and 0.86 (0.67 to 1.06), respectively. Threshold values discriminating responders and non-responders were 67% for SVV and 41% for PPV.ConclusionsIn intra-abdominal hypertension, respiratory variations in stroke volume and arterial pressure remain indicative of fluid responsiveness, even if threshold values identifying responders and non-responders might be higher than during normal intra-abdominal pressure. Further studies are required in humans to determine these thresholds in intra-abdominal hypertension.

Patient Mortality Is Associated With Staff Resources and Workload in the ICU: A Multicenter Observational Study.

Objective:Matching healthcare staff resources to patient needs in the ICU is a key factor for quality of care. We aimed to assess the impact of the staffing-to-patient ratio and workload on ICU mortality. Design:We performed a multicenter longitudinal study using routinely collected hospital data. Setting:Information pertaining to every patient in eight ICUs from four university hospitals from January to December 2013 was analyzed. Patients:A total of 5,718 inpatient stays were included. Interventions:None. Measurements and Main Results:We used a shift-by-shift varying measure of the patient-to-caregiver ratio in combination with workload to establish their relationships with ICU mortality over time, excluding patients with decision to forego life-sustaining therapy. Using a multilevel Poisson regression, we quantified ICU mortality-relative risk, adjusted for patient turnover, severity, and staffing levels. The risk of death was increased by 3.5 (95% CI, 1.3–9.1) when the patient-to-nurse ratio was greater than 2.5, and it was increased by 2.0 (95% CI, 1.3–3.2) when the patient-to-physician ratio exceeded 14. The highest ratios occurred more frequently during the weekend for nurse staffing and during the night for physicians (p < 0.001). High patient turnover (adjusted relative risk, 5.6 [2.0–15.0]) and the volume of life-sustaining procedures performed by staff (adjusted relative risk, 5.9 [4.3–7.9]) were also associated with increased mortality. Conclusions:This study proposes evidence-based thresholds for patient-to-caregiver ratios, above which patient safety may be endangered in the ICU. Real-time monitoring of staffing levels and workload is feasible for adjusting caregivers’ resources to patients’ needs.

Relative importance of flow versus pressure in splanchnic perfusion during cardiopulmonary bypass in rabbits.

Background Decreased gastrointestinal perfusion has been reported during cardiopulmonary bypass (CPB). Conflicting results have been published concerning thresholds of pressure and flow to avoid splanchnic ischemia during CPB. This study compared splanchnic perfusion during independent and randomized variations of CPB pump flow or arterial pressure. Methods Ten rabbits were studied during mild hypothermic (36°C) nonpulsatile CPB using neonatal oxygenators. Simultaneous measurements of tissue blood flow in four different splanchnic areas (gastric, jejunum, ileum, and liver) were performed by laser Doppler flowmetry (LDF) before CPB (T0) and during a 4-step factorial experimental block design. Pressure and flow were alternatively high or low in random order. Results Laser Doppler flowmetry was significantly lower than pre-CPB value but was better preserved (analysis of covariance) in all organs, except liver, when CPB flow was high, whatever the pressure. Splanchnic LDF values in the low-versus high-flow groups expressed as perfusion unit were (mean ± SD): stomach, 94 ± 66 versus 137 ± 75; jejunum, 118 ± 78 versus 172 ± 75; ileum, 95 ± 72 versus 146 ± 83; and liver, 79 ± 72 versus 108 ± 118. No significant difference of LDF was observed between the high- and low-pressure groups, whatever the flow, except for liver: stomach, 115 ± 64 versus 117 ± 83; jejunum, 141 ± 80 versus 148 ± 83; ileum, 127 ± 87 versus 114 ± 76; liver, 114 ± 88 versus 73 ± 70. Conclusion Prevention of splanchnic ischemia during CPB should focus on preservation of high CPB blood flow rather than on high pressure.

Utility of a point-of-care device for rapid determination of prothrombin time in trauma patients: a preliminary study.

BACKGROUND: Rapid and accurate determination of prothrombin time in trauma patients may help to faster control of bleeding induced coagulopathy. The goal of this prospective observational study was to investigate the accuracy of bedside measurements of prothrombin time by the mean of a point-of-care device (INRatio) in trauma patients. METHODS: Fifty blood samples were drawn at admission and during the acute care phase for standard coagulation assays (prothrombin time, International Normalized Ratio [INR], and fibrinogen) and INRatio testing (INRA) from 48 trauma patients. RESULTS: Standard coagulation assays were available after a mean of 66 minutes. Median Injury Severity Score was 18, and 16 patients (33%) had a coagulopathy. Significant correlation was found between INR and INRA (r: 0.93, 95% confidence interval: 0.87–0.96). The mean difference (bias) for INR was 0.00, and standard deviation (precision) of the difference was 0.78. However, in cases where there was decreased hemoglobin (<10 gr · L−1) and fibrinogen (<1.5 gr · L−1), bias and precision were increased. To predict the need for fresh frozen plasma transfusion (INR > 1.5), INRA cutoff value of 1.3 resulted in a sensitivity of 92% and a specificity of 79%. The area under the receiver operating characteristic curve was 0.946 (95% confidence interval: 0,845–0,982). CONCLUSION: INRatio may be a useful device in the management of trauma patients with ongoing or suspected coagulopathy that may help to save at least 60 minutes in the process of obtaining a prothrombin time result. It may allow earlier detection of coagulopathy and, together with vital sign and hemoglobin, may help to guide fresh frozen plasma transfusion.

Immediate Allergic Hypersensitivity to Quinolones Associates with Neuromuscular Blocking Agent Sensitization

BACKGROUND We identified a case of quinolone allergic hypersensitivity associated with quaternary ammonium (QA) sensitization, the allergic determinant of neuromuscular blocking agents (NMBAs). Concomitant sensitization to several chemically different drugs is rarely reported and raises the question of a nonfortuitous association. OBJECTIVE We evaluated a potential association between quinolone immediate allergic hypersensitivity and NMBA sensitization. METHODS QA-specific IgE detection was prospectively performed in 26 patients who presented an immediate hypersensitivity reaction to quinolones: 17 with a confirmed allergic hypersensitivity and 9 with allergic hypersensitivity not confirmed. We also included a control population of 88 outpatients without a history of quinolone or NMBA hypersensitivity. Patients with positive QA-specific IgE benefited from a NMBA allergologic workup. RESULTS The prevalence of positive QA-specific IgE was significantly higher in patients with quinolone allergic hypersensitivity (9/17, 53%) compared with patients with allergic hypersensitivity not confirmed (1/9, 11%) than in controls (3/88, 3.4%). In the quinolone allergic population, ofloxacin elicited inhibition of the 4 positive QA-specific IgE sera tested, in a dose-response manner. Among the 9 patients with positive QA-specific IgE, the QA sensitization (positivity of specific IgE) was confirmed by positive skin tests and/or basophil activation tests to at least 1 NMBA in 5 of the 7 tested patients. CONCLUSION We report here the first documentation of a high prevalence of QA sensitization in patients with quinolone allergic hypersensitivity. These results suggest a new way for NMBA sensitization. It thus seems appropriate to investigate NMBA sensitization when quinolone allergic hypersensitivity is diagnosed.

Complications digestives sévères après chirurgie cardiaque sous circulation extracorporelle

ObjectifÉvaluer l’incidence, les modalités de survenue et l’évolution des complications digestives après chirurgie cardiaque sous circulation extracorporelle (CEC).MéthodeÉtude rétrospective sur 6281 adultes opérés sous CEC entre le 1er janvier 1994 et le 31 décembre 1997.RésultatsSoixante patients ont présenté 68 complications digestives (1 %): hémorragie digestive haute (n = 23), ischémie intestinale (n = 19), cholécystite aiguë (n = 7), pancréatite aiguë (n = 6), dilatation colique (n = 13). L’incidence de ces complications, faible après chirurgie coronaire (0,4 %) ou valvulaire (0,8 %), était élevée après transplantation cardiaque (6 %) ou chirurgie d’une dissection aortique (9 %). Comparés à une population témoins, les patients ayant présenté une complication digestive avaient un score de Parsonnet plus élevé (29 ± 15 contre 13 ± 12 points, P = 0,002), étaient plus souvent opérés en urgence (40/60, 66 % contre 1120/6221, 18 %; P = 0,01), avaient subi une CEC plus longue (114 ± 66 contre 74 ± 42 min, P = 0,01), et avaient présenté plus fréquement un bas débit cardiaque postopératoire (45/60, 75 % contre 435/6221, 7 %; P = 0,001). La mortalité globale en présence d’une complication digestive a été de 52 %. Les facteurs associés à la mortalité étaient: survenue d’un sepsis (OR=38,7), survenue d’une insuffisance rénale (OR=7,9), âge > 75 ans (OR= 3,5), ventilation mécanique > 7 jours (OR=2,7), association d’une complication neurologique (OR=3,9).ConclusionLes complications digestives après CEC surviennent chez une population à risque. Ces complications s’intègrent dans un contexte de défaillance multiviscérale à l’origine d’une mortalité élevée.AbstractPurposeTo determine the incidence, circumstances of occurrence and evolution of gastrointestinal complications after cardiac surgery with extracorporeal circulation (ECC).MethodsRetrospective chart study of gastrointestinal complications in 6,281 patients undergoing ECC between January 1994 and December 1997.ResultsSixty patients developed 68 gastrointestinal complications (1%). Complications included: upper gastrointestinal bleeding (n = 23), intestinal ischemia (n = 19), cholecystitis (n = 7), pancreatitis (n = 6), and paralytic ileus (n = 16). The incidence of these complications was low after coronary artery (0.4%) or valvular surgery (0.8%) and high after cardiac transplantation (6%) and after surgery for acute aortic dissection (9%). Compared with a control population, patients with gastrointestinal complication had a higher Parsonnet score (29 ± 15 vs 13 ± 12 points; P = 0.002), were more frequently operated upon as an emergency (40/60, 66% vs 1120/6221, 18%; P = 0.01), underwent ECC of longer duration (114 ± 66 vs 74 ± 42 min; P = 0.01), and presented more frequently with low cardiac output after surgery (45/60, 75% vs 435/6221, 7%; P = 0.001). The mortality rate after gastrointestinal complications was 52%. The major factor associated with mortality was the occurence of sepsis (OR=38.7). Other factors were: renal failure (OR=7.9), age > 75 yr (OR=3.5), mechanical ventilation for more than seven days (OR=2.7), associated cerebral damage (OR=3.9).ConclusionGastrointestinal complications after ECC occur in high risk surgical patients. These complications are frequently associated with other complications leading to a high mortality rate.

Complications after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis: Risk factors for ICU admission and morbidity prognostic score

BACKGROUND AND OBJECTIVES For patients suffering from peritoneal carcinomatosis, cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is the only curative option. We focused on severe complications in the postoperative course of HIPEC. METHODS We studied perioperative data from patients who underwent HIPEC between January 2010 and August 2011. Our primary objective was to identify perioperative risk factors for ICU admission. Our secondary objective was to identify patient that may be re-admitted to the ICU thanks to a prognostic score. RESULTS 122 patients underwent HIPEC. 32 presented severe adverse events (26.2%) and 7 died (5.7%). Reasons for ICU admission were septic shock in 28.1% of patients, hemorrhagic shock for 21.9%, hemodynamic instability for 15.6%, respiratory causes for 6.2% and post-operative acidosis for 6.2%. Vasopressors were required for 34% and 40.6% were mechanically ventilated. CONCLUSION Peritoneal cancer index, diaphragmatic peritonectomy, the need of vasopressive therapy, total volume of fluid leakage collected in drains and total volume of fluid therapy administered at day 1 reported on ideal body weight were the 5 significant variables that we combined to build a morbidity prognostic score. One patient over 4 is likely to present severe complications. A predictive morbidity score provide informative data for clinicians.