To obtain preliminary evidence for the efficacy of lactoferrin as a preventative measure for noso... more To obtain preliminary evidence for the efficacy of lactoferrin as a preventative measure for nosocomial infections and inform the conduct of a definitive study. Phase 2, multicenter, randomized, double-blind, placebo-controlled study. Medical-surgical ICUs. Adult, critically ill patients receiving invasive mechanical ventilation. Randomized, eligible, consenting patients expected to require invasive mechanical ventilation more than 48 hours received lactoferrin both enterally and via an oral swab or a placebo of sterile water for up to 28 days. Of the 214 patients who were randomized, 212 received at least one dose of the intervention and were analyzed (107 lactoferrin and 105 placebo). Protocol adherence was 87.5%. Patients receiving lactoferrin were older (mean [SD], 66.3 [13.5] vs 62.5 [16.2] yr), had a higher Acute Physiology and Chronic Health Evaluation II score (26.8 [7.8] vs 23.5 [7.9]), and need for vasopressors (79% vs 70%). Antibiotic-free days (17.3 [9.0] vs 18.5 [7.1]; ...
Shorter-duration antibiotic treatment is sufficient for a range of bacterial infections, but has ... more Shorter-duration antibiotic treatment is sufficient for a range of bacterial infections, but has not been adequately studied for bloodstream infections. Our systematic review, survey, and observational study indicated equipoise for a trial of 7 versus 14 days of antibiotic treatment for bloodstream infections; a pilot randomized clinical trial (RCT) was a necessary next step to assess feasibility of a larger trial. We conducted an open, pilot RCT of antibiotic treatment duration among critically ill patients with bloodstream infection across 11 intensive care units (ICUs). Antibiotic selection, dosing and route were at the discretion of the treating team; patients were randomized 1:1 to intervention arms consisting of two fixed durations of treatment - 7 versus 14 days. We recruited adults with a positive blood culture yielding pathogenic bacteria identified while in ICU. We excluded patients with severe immunosuppression, foci of infection with an established requirement for prolon...
Clinicians&am... more Clinicians' current practice patterns in the management of acute respiratory distress syndrome (ARDS) and refractory hypoxemia are not well described. To describe mechanical ventilation strategies and treatment adjuncts for adults with ARDS including refractory hypoxemia. Prospective cohort study (March 2014-February 2015) of mechanically ventilated adults with moderate-to-severe ARDS requiring FiO2 ≥0.50 in 24 ICUs. We enrolled 664 patients: 222 (33%) with moderate and 442 (67%) with severe ARDS. On study day 1, mean tidal volume (VT) was 7.5 (SD2.1) ml/kg predicted body weight (n=625); 79% (n=496) received VT>6 ml/kg. Mean positive end-expiratory pressure (PEEP) was 10.5 (3.7) cmH2O (n=653); 568 patients (87%) received PEEP<15 cmH2O. Treatment adjuncts were common (n=440, 66%): neuromuscular blockers (n=276, 42%), pulmonary vasodilators (n=118, 18%), prone positioning (n=67, 10%), extracorporeal life support (n=29, 4%), and high-frequency oscillatory ventilation (n=29, 4%). Refractory hypoxemia, defined as PaO2<60 mmHg on FiO2 1.0, occurred in 138 (21%) patients. At onset of refractory hypoxemia, mean VT was 7.1 (2.0) ml/kg (n=127); 32 patients (26%) received VT>8 ml/kg. Mean PEEP was 12.1 (4.4) cmH2O (n=135); 99 patients (74%) received PEEP<15 cmH2O. Among patients with refractory hypoxemia, 91% received treatment adjuncts (126/138), with increased use of neuromuscular blockers (n=96, 70%), pulmonary vasodilators (n=62, 45%), and prone positioning (n=37, 27%). Patients with moderate-to-severe ARDS, receive treatment adjuncts frequently, especially with refractory hypoxemia. Paradoxically, therapies with less evidence supporting their use (e.g. pulmonary vasodilators) were over-utilized, while those with more evidence (e.g. prone positioning, neuromuscular blockade) were under-utilized. Patients received higher tidal volumes and lower PEEP than would be suggested by the evidence.
Background: Renin-angiotensin system (RAS) signaling and angiotensin-converting enzyme 2 (ACE2) h... more Background: Renin-angiotensin system (RAS) signaling and angiotensin-converting enzyme 2 (ACE2) have been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). We postulated that repleting ACE2 using GSK2586881, a recombinant form of human angiotensin-converting enzyme 2 (rhACE2), could attenuate acute lung injury.
Canadian journal of anaesthesia = Journal canadien d'anesthesie, Jan 14, 2017
Morphine is administered intravenously for pain management in the perioperative period. The effec... more Morphine is administered intravenously for pain management in the perioperative period. The effect of the inflammatory response to surgery on morphine distribution across the blood-brain barrier (BBB) in humans was investigated. We hypothesized that a graded surgically induced, systemic inflammatory response alters cerebrospinal fluid (CSF) levels of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) through a temporary reduction in BBB drug efflux transporter function. We conducted a prospective pharmacokinetic study of the plasma and CSF distribution of the P-glycoprotein (PGP) substrate morphine in 33 patients undergoing open thoracic (n = 18) or endovascular (n = 15) aortic aneurysm repair. Morphine was administered with induction of anesthesia and in the intensive care unit. Plasma and CSF concentrations of interleukin (IL)-6, morphine, M3G, M6G, and albumin were measured prior to surgery (baseline), during surgery, and postoperatively every six hours unti...
Canadian journal of anaesthesia = Journal canadien d'anesthesie, Jan 3, 2017
The purpose of this survey was to determine how Canadian healthcare professionals perceive their ... more The purpose of this survey was to determine how Canadian healthcare professionals perceive their deficiencies and educational requirements related to organ and tissue donation. We surveyed 641 intensive care unit (ICU) physicians, 1,349 ICU nurses, 1,561 emergency room (ER) physicians, and 1,873 ER nurses. The survey was distributed by the national organization for each profession (the Canadian Association of Emergency Physicians, the Canadian Association of Critical Care Nurses, and the National Emergency Nurses Association). Canadian Blood Services developed the critical care physician list in collaboration with the Canadian Critical Care Society. Survey development included questions related to comfort with, and knowledge of, key competencies in organ and tissue donation. Eight hundred thirty-one (15.3%) of a possible 5,424 respondents participated in the survey. Over 50% of respondents rated the following topics as highly important: knowledge of general organ and tissue donation...
... Accepted for publication June 23, 1997. Address correspondence to Dr. Richard Hall, Departmen... more ... Accepted for publication June 23, 1997. Address correspondence to Dr. Richard Hall, Department of An-aesthesia, Queen Elizabeth II Health Sciences Centre, NH1 Site, 1796 Summer St., Halifax, Nova Scotia, Canada B3H 3A7. 766 Anesth Analg 1997;85:766-82 ...
Some investigators believe that the dog is less sensitive than are humans to the anesthetic/analg... more Some investigators believe that the dog is less sensitive than are humans to the anesthetic/analgesic actions of opioids. The alfentanil plasma concentration [ALF] vs anesthetic effect relationship has been determined for humans undergoing surgery. This study was designed to determine the [ALF] vs anesthetic relationship for alfentanil in the enflurane-anesthetized dog and thereby to provide data by which the [ALF] vs anesthetic effect relationships in the dog and in humans could be compared. Mongrel dogs (n = 10) were anesthetized with enflurane, and enflurane MAC (EMAC) was determined in each dog. After this, each dog received at least three incremental infusions of alfentanil using infusion rates of 0.625, 1.6, 8, 32, or 80 micrograms.kg-1.min-1. EMAC and [ALF] were determined during each infusion rate. There was a linear increase in [ALF] produced by incremental infusions of alfentanil (r = 0.999). Administration of alfentanil produced a dose-dependent reduction of EMAC up to a maximum of 72.5 +/- 3.7% (mean +/- SEM) at 32 micrograms.kg-1.min-1 ([ALF] = 960 +/- 86 ng/ml); a ceiling effect was evident. The degree of EMAC reduction (69%) produced by an infusion rate of 8 micrograms.kg-1.min-1 ([ALF] = 223 +/- 13 ng/ml) was not statistically different from the EMAC reductions produced by infusion rates of 32 (73% reduction at [ALF] = 960 +/- 86 ng/ml) or 80 micrograms.kg-1.min-1 (70% reduction at [ALF] = 2613 +/- 247 ng/ml) (P greater than 0.05). The relative potency of alfentanil was one-seventh to one-tenth that of fentanyl studied under identical conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Purpose Recombinant activated factor VII (rFVIIa) is currently not approved by Health Canada or t... more Purpose Recombinant activated factor VII (rFVIIa) is currently not approved by Health Canada or the Food and Drug Administration for treating excessive blood loss in nonhemophiliac patients undergoing on-pump cardiac surgery, but is increasingly being used “off-label” for this indication. A Canadian Consensus Conference was convened to generate recommendations for rFVIIa use in on-pump cardiac surgery. Methods: The panel undertook a literature review of the use of rFVIIa in both cardiac and non-cardiac surgery. Appropriateness, timing, and dosage considerations were addressed for three cardiac surgery indications: prophylactic, routine, and rescue uses. Recommendationswere based on evidencefromtheliterature and derived by consensus following recognized grading procedures. Results The panel recommended against prophylactic or routine use of rFVIIa, as there is no evidence at this time that the benefits of rFVIIa outweigh its potential risks compared with standard hemostatic therapies. On the other hand, the panel made a weak recommendation (grade 2C) for the use of rFVIIa (one to two doses of 35–70 μg·kg-1) as rescue therapy for blood loss that is refractory to standard hemostatic therapies, despite the lack of randomized controlled trial data for this indication. Conclusions In cardiac surgery, the risks and benefits of rFVIIa are unclear, but current evidence suggests that its benefits may outweigh its risks for rescue therapy in selected patients. Methodologically rigorous studies are needed to clarify its risk-benefit profile in cardiac surgery patients. Objectif Le facteur VII activé recombinant (rFVIIa) n’est actuellement approuvé ni par Santé Canada ni par la Food and Drug Administration (FDA) pour le traitement du saignement excessif chez les patients non-hémophiles subissant une chirurgie cardiaque avec circulation extra-corporelle (CEC); néanmoins, il est de plus en plus utilisé de manière ‘non conforme’ pour cette indication. Une Conférence canadienne de consensus s’est réunie afin de rédiger des recommandations quant à l’utilisation du rFVIIa lors de la chirurgie cardiaque avec CEC. Méthode Le panel a entrepris une revue de la littérature traitant de l’utilisation du rFVIIa en chirurgies cardiaque et non cardiaque. Des considérations quant à la justification, au moment de l’administration et à la posologie ont été évaluées pour trois indications en chirurgie cardiaque: les utilisations prophylactique, de routine ou de sauvetage. Les recommandations, basées sur des données probantes tirées de la littérature, ont été interprétées par un consensus suivant des procédures de gradation reconnues. Résultats Le panel s’est prononcé contre une utilisation prophylactique ou de routine du rFVIIa, étant donné qu’il n’existe actuellement pas de preuve que les bienfaits du rFVIIa l’emportent sur les risques potentiels encourus en comparaison des thérapies hémostatiques standard. En revanche, le panel a énoncé une recommandation faible (note 2C) en faveur de l’utilisation du rFVIIa (une à deux doses de 35–70 μg·kg-1) comme thérapie de sauvetage en cas de saignement réfractaire aux thérapies hémostatiques standard et ce, malgré le manque de données d’études randomisées contrôlées concernant cette indication. Conclusion En chirurgie cardiaque, les risques et bienfaits du rFVIIa ne sont pas clairs; toutefois, les données actuelles suggèrent que ses bienfaits pourraient contrebalancer ses risques dans les cas de thérapie de sauvetage chez certains patients. Des études méthodologiquement rigoureuses sont nécessaires afin de clarifier le profil risque/bénéfice du rFVIIa pour les patients de chirurgie cardiaque.
Hypertonic sodium acetate-dextran solution (HAD) causes vasodilatation and buffers metabolic acid... more Hypertonic sodium acetate-dextran solution (HAD) causes vasodilatation and buffers metabolic acidosis. In controlled hemorrhage models, HAD in small volumes increases cardiac output without increasing blood pressure, thus creating a "high flow-low pressure" state. The objective of this study was to determine whether limited resuscitation of uncontrolled hemorrhage with HAD solution improves gut perfusion as measured by intestinal mucosal tonometry. Three groups of 10 swine were bled 25 mL/kg by means of a femoral artery catheter to produce a mean blood pressure of 30 mm Hg. A 4-mm abdominal aortic laceration was then produced by pulling out a preimplanted wire loop. Groups were then randomly assigned to be resuscitated with either lactated Ringer's solution, a hypertonic saline-dextran solution or HAD solution sufficient to maintain a mean blood pressure of 45 mm Hg for 5 hours or until death. Outcomes were measured by survival, intraperitoneal blood loss, hemodynamic ...
A projected increase in total hip arthroplasties, shortfalls in blood availability, and awareness... more A projected increase in total hip arthroplasties, shortfalls in blood availability, and awareness of complications of transfusion make blood management in orthopaedic surgery important. In a multicenter, randomized, double-blind, placebo-controlled study, we hypothesized use of aprotinin would reduce blood transfusions (any and allogeneic) and blood loss in total hip arthroplasty. Using an intent-to-treat approach, we recruited 393 patients stratified by preoperative autologous blood donation or none and then randomized them to receive aprotinin (176 patients receiving a 10,000 kallikrein inhibitor units [KIU] test dose, 2 million KIU load, 0.5 million KIU per hour) or placebo (177 patients). We assessed patients at baseline; postoperative days 1, 2, 3, and 7 (or discharge); and 6 +/- 2 weeks. Primary efficacy was percentage of patients having blood transfusion through day 7 or discharge. We based safety on reported adverse events. Aprotinin reduced transfusions by 46% (30 of 176 ve...
British journal of hospital medicine (London, England : 2005), 2015
Significant physiological changes are common among critically ill patients. This case-based revie... more Significant physiological changes are common among critically ill patients. This case-based review describes the consequences of these changes on the selection and dosing of medications.
To obtain preliminary evidence for the efficacy of lactoferrin as a preventative measure for noso... more To obtain preliminary evidence for the efficacy of lactoferrin as a preventative measure for nosocomial infections and inform the conduct of a definitive study. Phase 2, multicenter, randomized, double-blind, placebo-controlled study. Medical-surgical ICUs. Adult, critically ill patients receiving invasive mechanical ventilation. Randomized, eligible, consenting patients expected to require invasive mechanical ventilation more than 48 hours received lactoferrin both enterally and via an oral swab or a placebo of sterile water for up to 28 days. Of the 214 patients who were randomized, 212 received at least one dose of the intervention and were analyzed (107 lactoferrin and 105 placebo). Protocol adherence was 87.5%. Patients receiving lactoferrin were older (mean [SD], 66.3 [13.5] vs 62.5 [16.2] yr), had a higher Acute Physiology and Chronic Health Evaluation II score (26.8 [7.8] vs 23.5 [7.9]), and need for vasopressors (79% vs 70%). Antibiotic-free days (17.3 [9.0] vs 18.5 [7.1]; ...
Shorter-duration antibiotic treatment is sufficient for a range of bacterial infections, but has ... more Shorter-duration antibiotic treatment is sufficient for a range of bacterial infections, but has not been adequately studied for bloodstream infections. Our systematic review, survey, and observational study indicated equipoise for a trial of 7 versus 14 days of antibiotic treatment for bloodstream infections; a pilot randomized clinical trial (RCT) was a necessary next step to assess feasibility of a larger trial. We conducted an open, pilot RCT of antibiotic treatment duration among critically ill patients with bloodstream infection across 11 intensive care units (ICUs). Antibiotic selection, dosing and route were at the discretion of the treating team; patients were randomized 1:1 to intervention arms consisting of two fixed durations of treatment - 7 versus 14 days. We recruited adults with a positive blood culture yielding pathogenic bacteria identified while in ICU. We excluded patients with severe immunosuppression, foci of infection with an established requirement for prolon...
Clinicians&am... more Clinicians' current practice patterns in the management of acute respiratory distress syndrome (ARDS) and refractory hypoxemia are not well described. To describe mechanical ventilation strategies and treatment adjuncts for adults with ARDS including refractory hypoxemia. Prospective cohort study (March 2014-February 2015) of mechanically ventilated adults with moderate-to-severe ARDS requiring FiO2 ≥0.50 in 24 ICUs. We enrolled 664 patients: 222 (33%) with moderate and 442 (67%) with severe ARDS. On study day 1, mean tidal volume (VT) was 7.5 (SD2.1) ml/kg predicted body weight (n=625); 79% (n=496) received VT>6 ml/kg. Mean positive end-expiratory pressure (PEEP) was 10.5 (3.7) cmH2O (n=653); 568 patients (87%) received PEEP<15 cmH2O. Treatment adjuncts were common (n=440, 66%): neuromuscular blockers (n=276, 42%), pulmonary vasodilators (n=118, 18%), prone positioning (n=67, 10%), extracorporeal life support (n=29, 4%), and high-frequency oscillatory ventilation (n=29, 4%). Refractory hypoxemia, defined as PaO2<60 mmHg on FiO2 1.0, occurred in 138 (21%) patients. At onset of refractory hypoxemia, mean VT was 7.1 (2.0) ml/kg (n=127); 32 patients (26%) received VT>8 ml/kg. Mean PEEP was 12.1 (4.4) cmH2O (n=135); 99 patients (74%) received PEEP<15 cmH2O. Among patients with refractory hypoxemia, 91% received treatment adjuncts (126/138), with increased use of neuromuscular blockers (n=96, 70%), pulmonary vasodilators (n=62, 45%), and prone positioning (n=37, 27%). Patients with moderate-to-severe ARDS, receive treatment adjuncts frequently, especially with refractory hypoxemia. Paradoxically, therapies with less evidence supporting their use (e.g. pulmonary vasodilators) were over-utilized, while those with more evidence (e.g. prone positioning, neuromuscular blockade) were under-utilized. Patients received higher tidal volumes and lower PEEP than would be suggested by the evidence.
Background: Renin-angiotensin system (RAS) signaling and angiotensin-converting enzyme 2 (ACE2) h... more Background: Renin-angiotensin system (RAS) signaling and angiotensin-converting enzyme 2 (ACE2) have been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). We postulated that repleting ACE2 using GSK2586881, a recombinant form of human angiotensin-converting enzyme 2 (rhACE2), could attenuate acute lung injury.
Canadian journal of anaesthesia = Journal canadien d'anesthesie, Jan 14, 2017
Morphine is administered intravenously for pain management in the perioperative period. The effec... more Morphine is administered intravenously for pain management in the perioperative period. The effect of the inflammatory response to surgery on morphine distribution across the blood-brain barrier (BBB) in humans was investigated. We hypothesized that a graded surgically induced, systemic inflammatory response alters cerebrospinal fluid (CSF) levels of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) through a temporary reduction in BBB drug efflux transporter function. We conducted a prospective pharmacokinetic study of the plasma and CSF distribution of the P-glycoprotein (PGP) substrate morphine in 33 patients undergoing open thoracic (n = 18) or endovascular (n = 15) aortic aneurysm repair. Morphine was administered with induction of anesthesia and in the intensive care unit. Plasma and CSF concentrations of interleukin (IL)-6, morphine, M3G, M6G, and albumin were measured prior to surgery (baseline), during surgery, and postoperatively every six hours unti...
Canadian journal of anaesthesia = Journal canadien d'anesthesie, Jan 3, 2017
The purpose of this survey was to determine how Canadian healthcare professionals perceive their ... more The purpose of this survey was to determine how Canadian healthcare professionals perceive their deficiencies and educational requirements related to organ and tissue donation. We surveyed 641 intensive care unit (ICU) physicians, 1,349 ICU nurses, 1,561 emergency room (ER) physicians, and 1,873 ER nurses. The survey was distributed by the national organization for each profession (the Canadian Association of Emergency Physicians, the Canadian Association of Critical Care Nurses, and the National Emergency Nurses Association). Canadian Blood Services developed the critical care physician list in collaboration with the Canadian Critical Care Society. Survey development included questions related to comfort with, and knowledge of, key competencies in organ and tissue donation. Eight hundred thirty-one (15.3%) of a possible 5,424 respondents participated in the survey. Over 50% of respondents rated the following topics as highly important: knowledge of general organ and tissue donation...
... Accepted for publication June 23, 1997. Address correspondence to Dr. Richard Hall, Departmen... more ... Accepted for publication June 23, 1997. Address correspondence to Dr. Richard Hall, Department of An-aesthesia, Queen Elizabeth II Health Sciences Centre, NH1 Site, 1796 Summer St., Halifax, Nova Scotia, Canada B3H 3A7. 766 Anesth Analg 1997;85:766-82 ...
Some investigators believe that the dog is less sensitive than are humans to the anesthetic/analg... more Some investigators believe that the dog is less sensitive than are humans to the anesthetic/analgesic actions of opioids. The alfentanil plasma concentration [ALF] vs anesthetic effect relationship has been determined for humans undergoing surgery. This study was designed to determine the [ALF] vs anesthetic relationship for alfentanil in the enflurane-anesthetized dog and thereby to provide data by which the [ALF] vs anesthetic effect relationships in the dog and in humans could be compared. Mongrel dogs (n = 10) were anesthetized with enflurane, and enflurane MAC (EMAC) was determined in each dog. After this, each dog received at least three incremental infusions of alfentanil using infusion rates of 0.625, 1.6, 8, 32, or 80 micrograms.kg-1.min-1. EMAC and [ALF] were determined during each infusion rate. There was a linear increase in [ALF] produced by incremental infusions of alfentanil (r = 0.999). Administration of alfentanil produced a dose-dependent reduction of EMAC up to a maximum of 72.5 +/- 3.7% (mean +/- SEM) at 32 micrograms.kg-1.min-1 ([ALF] = 960 +/- 86 ng/ml); a ceiling effect was evident. The degree of EMAC reduction (69%) produced by an infusion rate of 8 micrograms.kg-1.min-1 ([ALF] = 223 +/- 13 ng/ml) was not statistically different from the EMAC reductions produced by infusion rates of 32 (73% reduction at [ALF] = 960 +/- 86 ng/ml) or 80 micrograms.kg-1.min-1 (70% reduction at [ALF] = 2613 +/- 247 ng/ml) (P greater than 0.05). The relative potency of alfentanil was one-seventh to one-tenth that of fentanyl studied under identical conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Purpose Recombinant activated factor VII (rFVIIa) is currently not approved by Health Canada or t... more Purpose Recombinant activated factor VII (rFVIIa) is currently not approved by Health Canada or the Food and Drug Administration for treating excessive blood loss in nonhemophiliac patients undergoing on-pump cardiac surgery, but is increasingly being used “off-label” for this indication. A Canadian Consensus Conference was convened to generate recommendations for rFVIIa use in on-pump cardiac surgery. Methods: The panel undertook a literature review of the use of rFVIIa in both cardiac and non-cardiac surgery. Appropriateness, timing, and dosage considerations were addressed for three cardiac surgery indications: prophylactic, routine, and rescue uses. Recommendationswere based on evidencefromtheliterature and derived by consensus following recognized grading procedures. Results The panel recommended against prophylactic or routine use of rFVIIa, as there is no evidence at this time that the benefits of rFVIIa outweigh its potential risks compared with standard hemostatic therapies. On the other hand, the panel made a weak recommendation (grade 2C) for the use of rFVIIa (one to two doses of 35–70 μg·kg-1) as rescue therapy for blood loss that is refractory to standard hemostatic therapies, despite the lack of randomized controlled trial data for this indication. Conclusions In cardiac surgery, the risks and benefits of rFVIIa are unclear, but current evidence suggests that its benefits may outweigh its risks for rescue therapy in selected patients. Methodologically rigorous studies are needed to clarify its risk-benefit profile in cardiac surgery patients. Objectif Le facteur VII activé recombinant (rFVIIa) n’est actuellement approuvé ni par Santé Canada ni par la Food and Drug Administration (FDA) pour le traitement du saignement excessif chez les patients non-hémophiles subissant une chirurgie cardiaque avec circulation extra-corporelle (CEC); néanmoins, il est de plus en plus utilisé de manière ‘non conforme’ pour cette indication. Une Conférence canadienne de consensus s’est réunie afin de rédiger des recommandations quant à l’utilisation du rFVIIa lors de la chirurgie cardiaque avec CEC. Méthode Le panel a entrepris une revue de la littérature traitant de l’utilisation du rFVIIa en chirurgies cardiaque et non cardiaque. Des considérations quant à la justification, au moment de l’administration et à la posologie ont été évaluées pour trois indications en chirurgie cardiaque: les utilisations prophylactique, de routine ou de sauvetage. Les recommandations, basées sur des données probantes tirées de la littérature, ont été interprétées par un consensus suivant des procédures de gradation reconnues. Résultats Le panel s’est prononcé contre une utilisation prophylactique ou de routine du rFVIIa, étant donné qu’il n’existe actuellement pas de preuve que les bienfaits du rFVIIa l’emportent sur les risques potentiels encourus en comparaison des thérapies hémostatiques standard. En revanche, le panel a énoncé une recommandation faible (note 2C) en faveur de l’utilisation du rFVIIa (une à deux doses de 35–70 μg·kg-1) comme thérapie de sauvetage en cas de saignement réfractaire aux thérapies hémostatiques standard et ce, malgré le manque de données d’études randomisées contrôlées concernant cette indication. Conclusion En chirurgie cardiaque, les risques et bienfaits du rFVIIa ne sont pas clairs; toutefois, les données actuelles suggèrent que ses bienfaits pourraient contrebalancer ses risques dans les cas de thérapie de sauvetage chez certains patients. Des études méthodologiquement rigoureuses sont nécessaires afin de clarifier le profil risque/bénéfice du rFVIIa pour les patients de chirurgie cardiaque.
Hypertonic sodium acetate-dextran solution (HAD) causes vasodilatation and buffers metabolic acid... more Hypertonic sodium acetate-dextran solution (HAD) causes vasodilatation and buffers metabolic acidosis. In controlled hemorrhage models, HAD in small volumes increases cardiac output without increasing blood pressure, thus creating a "high flow-low pressure" state. The objective of this study was to determine whether limited resuscitation of uncontrolled hemorrhage with HAD solution improves gut perfusion as measured by intestinal mucosal tonometry. Three groups of 10 swine were bled 25 mL/kg by means of a femoral artery catheter to produce a mean blood pressure of 30 mm Hg. A 4-mm abdominal aortic laceration was then produced by pulling out a preimplanted wire loop. Groups were then randomly assigned to be resuscitated with either lactated Ringer's solution, a hypertonic saline-dextran solution or HAD solution sufficient to maintain a mean blood pressure of 45 mm Hg for 5 hours or until death. Outcomes were measured by survival, intraperitoneal blood loss, hemodynamic ...
A projected increase in total hip arthroplasties, shortfalls in blood availability, and awareness... more A projected increase in total hip arthroplasties, shortfalls in blood availability, and awareness of complications of transfusion make blood management in orthopaedic surgery important. In a multicenter, randomized, double-blind, placebo-controlled study, we hypothesized use of aprotinin would reduce blood transfusions (any and allogeneic) and blood loss in total hip arthroplasty. Using an intent-to-treat approach, we recruited 393 patients stratified by preoperative autologous blood donation or none and then randomized them to receive aprotinin (176 patients receiving a 10,000 kallikrein inhibitor units [KIU] test dose, 2 million KIU load, 0.5 million KIU per hour) or placebo (177 patients). We assessed patients at baseline; postoperative days 1, 2, 3, and 7 (or discharge); and 6 +/- 2 weeks. Primary efficacy was percentage of patients having blood transfusion through day 7 or discharge. We based safety on reported adverse events. Aprotinin reduced transfusions by 46% (30 of 176 ve...
British journal of hospital medicine (London, England : 2005), 2015
Significant physiological changes are common among critically ill patients. This case-based revie... more Significant physiological changes are common among critically ill patients. This case-based review describes the consequences of these changes on the selection and dosing of medications.
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Papers by Richard I Hall