ANALGOSEDATION IN HUMANS: WHAT TO CHOOSE?

Analgo-sedation implies the use of intravenous drugs for analgesia and sedation in patients undergoing outpatient operations or one-day surgery, in which vital signs (SpO2, NIBP, HR, RR, EtCO2) are steadily supervised (1,2). Sedation and analgesia are different conditions: some patients may only need sedation, others only analgesia or both. Analgo-sedation allows the operator to work in the most favorable conditions, given that the patient becomes collaborative, extremely quiet and compliant with the procedure, even in cases of hours long procedures, all carried in absolute safety. Milestones in analgo-sedation: Between the 1920’s and the mid 1950’s the only drugs used as sedatives and hypnotics were barbiturates (Somnifen®, Pernocton®, Pentothal®, Evipal®, etc.). The use of barbiturates declined in the 1950’s after the development of the benzodiazepine derivatives. In 1959, De Castro and Mundeleer introduced the concept of neuroleptoanalgesia followed by the release of "Innovar®", a 50:1 combination of droperidol and fentanyl, both originally synthesized by Janssen pharmaceuticals, which was followed on the Italian market by “Leptofen®” (Famitalia). The next advance in analgosedation at the end of 70s, was the release of the steroid anesthetic "Althesin®", a surprising combination of the two steroidal compounds, alfaxalone and alfadolone. In spite of its deplorable histamine release, althesin safety profile due to its highest (30/1) therapeutic index among all anesthetic molecules, bestowed to it a long-lasting popularity. The advent of noncumulative anesthetic molecules brought the new concept of TIVA (Total Intravenous Anesthesia) in the field of analgosedation. Most of this unexpected innovation was due to the hypnotic alkylphenol derivative Propofol® and to the opioid agonist remifentanil hydrochloride, both characterized by fast and alternative metabolic pathways. In virtue of their pharmacodynamics and pharmacokinetics peculiarities, propofol and remifentanil, administered by TCI (Target Controlled Infusion), are nowadays the ideal drugs for analgosedation (3). Administered by TCI, such hypnotic/opioid combination warrants extreme precision in dose titration, fast and predictable variations in analgo-sedation depth, reduction of total administered dose, very fast recovery of consciousness and reduction of hospitalization times. Currently, Remimazolam, a new benzodiazepine now in phase III of clinical experimentation, seems to promise further development and enhancement to the current analgo-sedation techniques (4). It is worth to note that parallel advancement in veterinary analgosedation was provided in the same years by parallel anesthetic formulations named pentothal vet®, Innovar vet®, Saffan® (alfaxalone and alfadolone), Rapinovet® (propofol), and by the off label use of most of the formulations of the anesthetic molecules approved for use in humans

Preoperative intraaortic balloon pumping improves outcomes for high-risk patients in routine coronary artery bypass graft surgery

BACKGROUND: We evaluated the association between the preoperative use of intraaortic balloon pumping and in-hospital and long-term outcomes in high-risk patients undergoing coronary artery bypass grafting. METHODS: From 714 total patients undergoing coronary artery bypass grafting during a 4-year period, we compared the clinical, biochemical, and echocardiographic findings up to 1 year after surgery between 111 patients who had a European System for Cardiac Operative Risk Evaluation (EuroSCORE) of 12 or greater and received intraaortic balloon pumping preoperatively (group A) and 130 patients who had a EuroSCORE of 5 or less and received no preoperative intraaortic balloon pumping (group B). RESULTS: Group A patients were significantly older, had significantly more comorbid conditions, and had a significantly lower mean preoperative ejection fraction (all p < 0.001). Intraoperative data were comparable between groups, as were lactate and troponin I levels sampled from the coronary sinus. Lactate, troponin I, creatine kinase, and creatine kinase-MB mass showed comparable leakage at all postoperative times. The incidences of in-hospital mortality, perioperative myocardial damage, and acute myocardial infarction and duration of hospital stay were comparable. High-risk patients showed significant improvements in ejection fraction (p < 0.001) and wall-motion score index (p = 0.06) after surgery, but low-risk patients showed no significant change in these variables. The incidences of death, recurrent angina, myocardial infarction, and repeat coronary procedures did not differ significantly between groups. CONCLUSIONS: The preoperative use of intraaortic balloon pumping appears to shift high-risk patients undergoing coronary artery bypass grafting into a lower-risk category and is associated with comparable perioperative troponin leakage and short-term and long-term outcomes similar to low-risk patients not receiving intraaortic balloon pumping

Troponin I and lactate from coronary sinus predict cardiac complications after myocardial revascularization

Background. Postoperative troponin I and lactate elevation are related to cardiac complications after myocardial revascularization. We sought to evaluate earlier predictive value for acute myocardial infarction (AMI) and myocardial damage of troportin I and lactate after myocardial revascularization.Methods. In all, 183 consecutive isolated myocardial revascularizations were prospectively enrolled in the study. Troportin I and lactate were sampled preoperatively and intraoperatively from the coronary sinus, and at 12, 24, 48, and 72 hours. Hospital outcome was recorded. Receiver operating curves for coronary sinus troponin I and lactate were constructed to differentiate patients with or without AMI and myocardial damage.Results. Acute myocardial infarction developed in 6 patients (3.2%), with higher troponin I and lactate at all time points (p &lt; 0.05), longer intubation time (p = 0.003), intensive care unit stay (p = 0.001), hospital stay (p = 0.001), higher atrial fibrillation (p = 0.001), and worse ventricular function (p = 0.001). Myocardial damage developed in 6 patients (3.2%), showing higher troponin I at all time points (p &lt; 0.001), higher intraoperative lactate (P = 0.04), longer intubation time (p = 0.005), and intensive care unit stay (p = 0.03). Receiver operating characteristic curves demonstrated coronary sinus troponin I greater than 0.94 mu g/L (area under the curve [AUCI 0.820 +/- 0.075; sensitivity 90.0%, specificity 68.9%) as a better discriminator between patients with or without AMI than lactate level greater than 2.85 mmol/L (AUC 0.686 +/- 0.090; sensitivity 80.0%; specificity 72.9%); troponin I greater than 0.65 mu g/L was a better discriminator between patients with or without myocardial damage (AUC 0.834 +/- 0.061; sensitivity 93.8%, specificity 71.5%), than lactate greater than 2.05mmol/L (AUC 0.627 +/- 0.067; sensitivity 87.5%; specificity 70.7%).Conclusions. Coronary sinus troponin I and lactate are predictive for cardiac complications after myocardial revascularization. Intraoperative biochemical assays should be routinely performed to establish preventative strategies to reduce further myocardial damage

Transbrachial insertion of a 7.5-Fr intra-aortic balloon pump in a severely atherosclerotic patient

Objective: Preoperative intra-aortic balloon pumping (IABP) improves the results of complex coronary surgery. However, its insertion may be harmful or contraindicated in cases of severe and diffuse atherosclerosis of the descending aorta and peripheral arteries. We sought to evaluate the efficacy and safety of transbrachial insertion of the new 7.5-Fr IABP to support a severely ill patient with eggshell distal aorta and femoro-iliac arteries undergoing coronary artery bypass grafting (CABG).Design. Case report.Setting: An 18-bed adult cardiac surgery unit at a university hospital.Patient A 68-yr-old man with ongoing unstable angina, left main disease, and eggshell calcification in the abdominal aorta and iliacofemoral arteries, needing IABP for CABG.Intervention., Percutaneous sheathless right transbrachial insertion of 7.5-Fr IABP, followed by CABG.Measurements and Main Results. Fluoroscopy and chest radiograph were used to confirm the exact position of the IABP, in the preoperative and postoperative time, respectively. A digital pulse oximeter was applied to monitor distal perfusion. Anticoagulation consisted of nadroparin 4000 lU daily until the second postoperative day, followed by 150 mg of aspirin daily thereafter. Transbrachial IABP support allowed uneventful CABG and postoperative course, without IABP-related complications. Pulse oximetry demonstrated constant good values, the radial artery pulse was always present, and the hand appeared constantly warm. IABP was withdrawn 20 hrs following surgery, and the patient was discharged home on the ninth postoperative day.Conclusions. The miniaturization of IABP, with the recent introduction of a 7.5-Fr balloon catheter, opens the door for the safe, effective transbrachial method of insertion in patients with severe peripheral atherosclerosis

Pulsatile perfusion with intra-aortic balloon pumping ameliorates whole body response to cardiopulmonary bypass in the elderly

Objective: The growing life expectancy has led the elderly to be increasingly referred to coronary artery bypass grafting. Preexisting comorbidities may benefit from theoretical advantages of pulsatile perfusion during cardiopulmonary bypass (CPB).Design: Prospective randomized trial.Setting: Cardiac surgery unit in a university hospital.Patients. Eighty consecutive patients older than 70 years.Interventions: Elective coronary artery bypass grafting on CPB, randomizing to conventional linear CPB (40 patients, group A) or intra-aortic balloon pump (IABP)-induced pulsatile CPB (40 patients, group B).Measurements and Main Results: We evaluated hemodynamic response by pulmonary artery flotation catheter, metabolic/splanchnic response by lactate and transaminase, bilirubin, amylase, and renal function (creatinine clearance, creatinine, incidence of renal insufficiency and failure), respiratory response by Pao(2)/Fio(2), respiratory compliance, scoring of chest radiograph, intubation time, and need for noninvasive positive-pressure ventilation, hematologic response by chest drainage, hemocoagulative and fibrinolytic cascades, and transfusions. IABP-related complications were recorded. Two minor IABP-related complications (2.5%) were registered. Hemodynamics was comparable, except for a slightly better cardiac index and indexed systemic vascular resistances at the end of CPB and at intensive therapy unit (ITU) admission (p &lt; 0.05). Transaminases, bilirubin, amylase, proved lower in group B (p &lt; 0.05 from ITU admission to 48 hours). Creatinine clearance, serum creatinine, and lactate were better in group B (p &lt; 0.05), and acute renal insufficiency was accordingly lower (p = 0.02). Respiratory response demonstrated better Pao(2)/Fio(2) and respiratory compliance from aortic declamping to 48 hours, with better scoring of chest radiograph (p &lt; 0.05 from ITU admission to 48 hours), lower noninvasive positive-pressure ventilation (p = 0.002) and intubation time (p = 0.031) in group B. Lower chest drainage (p &lt; 0.05 at first and second day), transfusions (p &lt; 0.05), activated partial thromboplastin time, international normalized ratio, white blood cells, and D-dimer (p &lt; 0.05 from ITU admission to 48 hours), together with higher platelets, fibrinogen, and antithrombin III (p &lt; 0.05 from ITU admission to 48 hours) were demonstrated in the pulsated group.Conclusions. IABP-induced pulsatile flow significantly improves whole body perfusion in the elderly undergoing CPB. (Crit Care Med 2009; 37:902-911

The Anticonvulsant Activity of a Flavonoid-Rich Extract from Orange Juice Involves both NMDA and GABA-Benzodiazepine Receptor Complexes

The usage of dietary supplements and other natural products to treat neurological diseases has been growing over time, and accumulating evidence suggests that flavonoids possess anticonvulsant properties. The aim of this study was to examine the effects of a flavonoid-rich extract from orange juice (OJe) in some rodent models of epilepsy and to explore its possible mechanism of action. The genetically audiogenic seizures (AGS)-susceptible DBA/2 mouse, the pentylenetetrazole (PTZ)-induced seizures in ICR-CD1 mice and the WAG/Rij rat as a genetic model of absence epilepsy with comorbidity of depression were used. Our results demonstrate that OJe was able to exert anticonvulsant effects on AGS-sensible DBA/2 mice and to inhibit PTZ-induced tonic seizures, increasing their latency. Conversely, it did not have anti-absence effects on WAG/Rij rats. Our experimental findings suggest that the anti-convulsant effects of OJe are likely mediated by both an inhibition of NMDA receptors at the glycine-binding site and an agonistic activity on benzodiazepine-binding site at GABAA receptors. This study provides evidences for the antiepileptic activity of OJe, and its results could be used as scientific basis for further researches aimed to develop novel complementary therapy for the treatment of epilepsy in a context of a multitarget pharmacological strategy