Farmacología perioperatoria

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Presentación sobre farmacología perioperatoria presentada en el Congreso Iberoamericano de Medicina Interna en Cancún, México el 27 de Noviembre del 2010.
Revisión de las generalidades del paciente quirúrgico y sus implicaciones en la farmacología perioperatoria.
Revisión del manejo de medicamentos cardiovasculares, psiquiátricos, antiplaquetarios, anticoagulantes, vitaminas y suplementos, etc.

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  • Analyze the risks and benefits underlying perioperative management of antiplatelet and anticoagulant medications.
    Recognize the importance of continuing most cardiovascular medications perioperatively.
    Recognize the importance of continuing most pulmonary medications perioperatively.
    Assess when stress dose steroids are indicated and manage other endocrine medications in the perioperative period.
    List the theoretical risks of continuing neuropsychiatric medications and decide whether or not to discontinue them.
    Identify and discontinue herbal medications that may adversely impact perioperative outcomes.
  • At least 50% percent of patients undergoing surgery take medications on a regular basis
    Clinicians often must decide if chronic medications should be continued in the perioperative period.
    Unfortunately, there are few outcome data about the majority of medications taken in the perioperative period.
  • Existe variacion sustancial entre diferentes medicos
    La experiencia clinica es la base mas importante de las recomendaciones
    Hay que entender la farmacocinetica de los medicamentos en la etapa perioperatoria asi como el riesgo potencial de su administracion – sangrado, hipoglucemia
    Considerar los beneficios potenciales del inicio de nuevos medicamentos de manera profilactica para prevenir isquemia (betabloqueadores), trombosis (anticoagulantes), infeccion de herida quirurgica (antibioticos), aspiracion (NPO)
    Los medicamentos recomendados en la mañana de la cirugia se deben dar con unos sorbos de agua.
  • The metabolism and elimination of medications and their metabolites may be altered during the perioperative period.
    Intravenous, transdermal, or transmucosal medicines should be substituted when absorption will be impaired because of loss of gastrointestinal function or restrictions on oral intake.
  • Medications associated with known medical morbidity if withdrawn abruptly should be continued in the perioperative period, or tapered if feasible.
    Stress response to surgery. Decisions about perioperative drug therapy should always take into account the stress response to surgery and the challenge it presents to homeostasis in the face of increased sympathetic tone and release of pituitary hormones.
    Medications not meeting either of the above principles can be discontinued or continued based on clinician judgment.
    The many medications administered perioperatively during a relatively short period increase the potential for drug-drug interactions.
    In a prospective medication survey of 1,025 patients admitted to a general surgery unit in New Zealand, Kennedy et al reported that 49% of the patients were taking medications (other than vitamins) unrelated to their surgical procedure.
    • The odds ratio for a postoperative complication was 2.7 (95% CI, 1.76–4.04) if patients were taking a drug unrelated to their surgery.
    • The risk of a complication was particularly elevated:
    - if patients were taking cardiovascular drugs or agents that act on the central nervous system;
    - if patients were on NPO (“nothing by mouth”) orders for more than 24 hours before surgery; and if the operation was more than 1 hour in duration.
    These findings could reflect destabilization of the disease processes for which the patients were taking chronic medications that required interruption.
  • Marik (Thomas Jefferson in Philadelphia) - A recent systematic literature review concluded that continuation of chronic corticosteroid
    therapy without supplemental (stress) doses of corticosteroids is appropriate unless patients have primary disease of the hypothalamic-pituitary-adrenal axis, in which case perioperative stress dosing is recommended to avoid acute adrenal insufficiency (addisonian crisis).
  • Stopping a chronic medication for a surgical procedure raises the possibility that its resumption could be overlooked,
    especially since medical errors are particularly common in the transition between health care settings following hospital discharge.
    A population-based cohort study among all elderly patients discharged from Ontario, Canada, hospitals over a 5½-year period found
    that 11.4% of patients undergoing elective surgery did not resume their indicated chronic warfarin therapy within 6 months after its presurgical discontinuation.
    Although 6-month rates of unintended failure to resume therapy were lower for statins (4%) and ophthalmic beta-blocker drops (8%),5 these findings underscore that drug discontinuation always carries a risk that therapy might not be resumed as indicated.
    Patients prescribed long-term therapy with warfarin were at risk for potentially unintended medication discontinuation after elective procedures. Patients prescribed statins or -blocker ophthalmic drops were not at increased risk.
    The development of post-operative renal or liver failure may affect the reutilization
  • Take-away general principles
    The following principles can be applied to guide perioperative medication management in a general sense7:
    • Continue medications with withdrawal potential
    • Discontinue medications that increase surgical risk and are not essential for short-term quality of life
    • Use clinical judgment when neither of the above two principles applies, but be mindful that many other medications are given in the narrow perioperative time window and that metabolism and elimination of chronic drugs may be altered.
  • Mayor sensibilidad a fármacos:
    ↓ [albúmina]sérica
    ↓ flujo sanguíneo hepático
  • 1) The first factor, CO, affects drug distribution and dilution in the first minute after administration. Mammillary compartment models assume that drugs mix instantaneously in the central compartment and then decline according to a multiexponential disposition function.
    Because these models underestimate early peak concentrations, they cannot characterize how changes in early distribution affect dose requirements. Physiological pharmacokinetics and recirculatory models can accurately describe the effects of variables such as CO on early drug distribution [1–3].
    For example, Wada’s physiological model predicts that an obese patient’s increased CO requires administration of a thiopental dose 46% higher than would be required for an average-sized person to attain the same peak-plasma concentration.
    2) The second factor is increased LBW. The LBW/total body weight (TBW) ratio is lower in obese patients than in normal-weight patients. However, obese patients’ LBW exceeds that of normal-weight patients, accounting for 20–40% of the obese patient’s excess body weight. In general, absolute clearance is greater in obese than in nonobese patients, increasing nonlinearly with TBW, but linearly with LBW, implying that drug clearance is similar after normalizing for LBW [4] and also implying that LBW is a key factor when adjusting a maintenance drug dose for a morbidly obese patient. In addition, in the morbidly obese patients, a higher correlation between CO and LBW exists than between CO and fat tissue mass [5], suggesting the significance of LBW not only for determining maintenance dosing but also for determining loading and induction doses.
    - Finally, LBW is TBW minus body fat weight. When TBW increases, LBW also increases taking into account changes in body composition associated with obesity depending on TBW, height, and sex. LBW is also significantly correlated with CO, an important factor in the early distribution kinetics. Most metabolic activity occurs in the lean tissues, and clearance increases linearly with LBW. Therefore, LBW as a dosing scalar is valid across all body compositions. -- Superior to ideal body weight, body mass index, body surface area
    3) The third factor is the increased fat mass; the increased fat mass of morbidly obese patients is poorly perfused. In a normal-weight patient, blood flow to fat equals 5% of the CO, whereas in an obese patient it equals only 2% of CO. Decreased fat perfusion may explain why the volume of distribution of lipophilic agents does not increase proportionally to the increased fat mass.
    4) The fourth factor is increased extracellular fluid volume. Because adipose tissue’s water content is almost completely extracellular, in obese patients, extracellular fluid volume and the ratio of extracellular to intracellular fluid volume are increased, thereby increasing the distribution volume of hydrophilic substances such as muscle relaxants.
  • - Finally, LBW is TBW minus body fat weight. When TBW increases, LBW also increases taking into account changes in body composition associated with obesity depending on TBW, height, and sex. LBW is also significantly correlated with CO, an important factor in the early distribution kinetics. Most metabolic activity occurs in the lean tissues, and clearance increases linearly with LBW. Therefore, LBW as a dosing scalar is valid across all body compositions. -- Superior to ideal body weight, body mass index, body surface area
  • Patients believed to be at high risk for perioperative vascular complications in whom perioperative hemorrhage would result in minimal morbidity should continue aspirin. This includes patients on maintenance aspirin therapy who have coronary stents or who are undergoing CABG or peripheral arterial surgery [68-70]. A 2007 update of a 2004 ACC/AHA task force recommended that aspirin should not be withheld before either elective or nonelective CABG after ST elevation MI [77].
    2008 AACP - Bare metal coronary stent who require surgery within 6 weeks of stent placement, we recommend continuing aspirin and clopidogrel in the perioperative period (Grade 1C);
    Drug-eluting coronary stent who require surgery within 12 months of stent placement, we recommend continuing aspirin and clopidogrel in the perioperative period (Grade 1C).
  • Continue/discontinue — There are no data on the safety of dipyridamole if continued in the perioperative period. Like aspirin, factors to consider in deciding whether to continue or hold dipyridamole reflect a balance between the risk of bleeding and risk of ischemic events. If discontinued, the drug should be stopped at least two days before surgery. Aggrenox (combination aspirin and dipyridamole) should be discontinued seven to ten days before surgery.
    Many patients take both aspirin and thienopyridine therapy to prevent coronary stent thrombosis. Premature cessation of thienopyrindine therapy is associated with an increased risk for stent thrombosis. Except for emergent settings, we recommend that surgery be delayed and therapy with thienopyridine and aspirin be continued for at least the minimum recommended duration for each stent type (one month for bare metal stents and ideally up to 12 months for drug eluting stents).
    If surgery must be performed before these minimum time periods, it is best to consult with the treating cardiologist and surgeon. If the risk of major bleeding appears greater than the risk of stent thrombosis, thienopyridine therapy should be discontinued for as brief a period as possible.
  • For most NSAIDs, platelet function normalizes within three days of discontinuation, suggesting that NSAIDs should be discontinued at least three days before surgery; ibuprofen can be stopped 24 hours prior to surgery.
  • 2008 ACCP guidelines on antithrombotic therapy recommend resuming aspirin approximately 24 hours (or the next morning) after surgery when there is adequate hemostasis [78].
    Formulations/alternatives — Aspirin is not available in parenteral forms, but is available as a rectal suppository for patients who are felt to need ongoing therapy but cannot take oral medication.
  • but was not associated with a significant increase in potentially sight-threatening local anaesthetic or operative haemorrhagic complications.
  • Restorations Mohs’ surgery Diagnostic esophagogastroduodenoscopy
    Uncomplicated extractions Simple excisions Colonoscopy without biopsy
    Endodontics Diagnostic endoscopic retrograde cholangiopancreatography
    Prosthetics Biliary stent without sphincterotomy
    Periodontal therapy Endoscopic ultrasonography without biopsy
    Dental hygiene
  • The primary mechanism of action of the established anticoagulants (unfractionated heparin [UFH], low-molecularweight heparin [LMWH], and fondaparinux) via antithrombin dependent binding (A) and the new anticoagulants (rivaroxaban, apixaban, and dabigatran etexilate) via antithrombin-independent binding (B). UFH also inactivates factors Xa, IXa, XIa, and XII via antithrombin, but to a lesser extent than inactivation of thrombin. LMWH also inactivates thrombin via antithrombin, but to a lesser extent than inactivation of factor Xa. AT antithrombin
  • Revisión sistematica con metaanálisis de efectos aleatorios (incoropora la variabilidad intra-estudio e inter-estudio)
    5 studies; N = 434
    Preoperative RAAS-antagonists on the day of surgery – increased likelihood of ↓BP requiring vasopressors after induction (RR 1.50, 95% CI 1.15 to 1.96).
  • In general, antihypertensive medications are continued perioperatively. There is some evidence that they may minimize blood pressure lability, particularly with laryngoscopy and intubation. Certain antihypertensive drugs are associated with adverse effects if stopped abruptly. β-blocker cessation has resulted in rebound hypertension and ischemic events, and clonidine is well-known for rebound hypertension if it is discontinued acutely.
    β-blockers have been shown to reduce myocardial ischemia and perioperative nonfatal myocardial infarctions,13 and all patients currently taking β blockers should continue them perioperatively to prevent rebound ischemia and hypertension.14 The recommendations for starting β-blockers prophylactically15 are less clear in view of the adverse outcomes of increased stroke and all-cause mortality in the POISE (Perioperative Ischemic Evaluation Study) trial.16 Please see our Perioperative Cardiac Risk Management module for more detailed information.
  • The prespecifed primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal cardiac arrest at 30 days after randomisation
  • Retrospective cohort study of patients 18 years of age or older who underwent major noncardiac surgery in 2000 and 2001 at 329 hospitals throughout the United
    States.
    Propensity-score matching was used to adjust for differences between patients who received perioperative beta-blockers and those who did not receive such therapy and compared in-hospital mortality using multivariable logistic modeling.
    N = 782,969 patients,
    663,635 (85 percent) had no recorded contraindications to beta-blockers,
    - 122,338 of whom (18 percent) received such treatment during the first two hospital days
  • Objectives: This study evaluated timing of β-blocker initiation before surgery and its relationship with: 1) pre-operative heart rate and high-sensitivity C-reactive-protein (hs-CRP) levels; and 2) post-operative outcome.
    N = 940 vascular surgery patients, pre-operative heart rate and hs-CRP levels were recorded, next to timing of β-blocker initiation before surgery (0 to 1, >1 to 4, >4 weeks). Pre- and post-operative troponin-T measurements and electrocardiograms were performed routinely. End points were 30-day cardiac events (composite of myocardial infarction and cardiac mortality) and long-term mortality. Multivariate regression analyses, adjusted for cardiac risk factors, evaluated the relation between duration of β-blocker treatment and outcome.
    Results: The β-blockers were initiated 0 to 1, >1 to 4, and >4 weeks before surgery in 158 (17%), 393 (42%), and 389 (41%) patients, respectively. Median heart rate at baseline was 74 (±17) beats/min, 70 (±16) beats/min, and 66 (±15) beats/min (p < 0.001; comparing treatment initiation >1 with <1 week pre-operatively), and hs-CRP was 4.9 (±7.5) mg/l, 4.1 (±.6.0) mg/l, and 4.5 (±6.3) mg/l (p = 0.782), respectively. Treatment initiated >1 to 4 or >4 weeks before surgery was associated with a lower incidence of 30-day cardiac events (odds ratio: 0.46, 95% confidence interval [CI]: 0.27 to 0.76, odds ratio: 0.48, 95% CI: 0.29 to 0.79) and long-term mortality (hazard ratio: 0.52, 95% CI: 0.21 to 0.67, hazard ratio: 0.50, 95% CI: 0.25 to 0.71) compared with treatment initiated <1 week pre-operatively.
    Conclusions: Our results indicate that β-blocker treatment initiated >1 week before surgery is associated with lower pre-operative heart rate and improved outcome, compared with treatment initiated <1 week pre-operatively. No reduction of median hs-CRP levels was observed in patients receiving β-blocker treatment >1 week compared with patients in whom treatment was initiated between 0 and 1 week before surgery.
  • β-blockers have been shown to reduce myocardial ischemia and perioperative nonfatal myocardial infarctions,13 and all patients currently taking β blockers should continue them perioperatively to prevent rebound ischemia and hypertension.14 The recommendations for starting β-blockers prophylactically15 are less clear in view of the adverse outcomes of increased stroke and all-cause mortality in the POISE (Perioperative Ischemic Evaluation Study) trial.16 Please see our Perioperative Cardiac Risk Management module for more detailed information.
  • As per the American College of Cardiology guidelines,15 statins should be continued in patients already taking them despite the recommendations of the drug manufacturers to stop them preoperatively. In general, most observational studies have reported favorable effects (fewer cardiac events or deaths) in patients on statins compared with those not on a statin and worse outcomes for patients whose statins were stopped.26 One small prospective randomized-controlled trial27 showed a benefit in a composite cardiovascular outcome in patients started on atorvastatin prophylactically. A larger, but yet unpublished study (DECREASE III [Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography]) showed that prophylactic fluvastatin-reduced ischemia, nonfatal myocardial infarction, and death in vascular surgery patients. The underpowered DECREASE IV trial showed a non-significant trend toward fewer major cardiac complications with prophylactic fluvastatin in intermediate-risk patients.28 Statins may also reduce venous thromboembolism.29 The theoretical concerns of possible rhabdomyolysis and liver toxicity have not been demonstrated, and perioperative statins appear to be safe.30 Non-statin lipid-lowering agents have theoretical potential for adverse effects: cholestyramine may decrease absorption of other medications,31 and gemfibrozil and niacin may be associated with myopathy and rhabdomyolysis. Due to their potential adverse effects and lack of data showing perioperative benefits, these medications are usually discontinued before surgery.
  • Antianginal medications should be continued to minimize the chance of perioperative ischemia. These medications include nitrates, β-blockers, and calcium channel blockers.
    Antiarrhythmic drugs should also be continued perioperatively for rhythm and rate control.
  • The landmark study by Van den Berghe et al of intensive insulin therapy in surgical ICU patients demonstrated signifi cant reductions in morbidity and mortality when glucose levels were controlled aggressively (80 to 110 mg/ dL; average, 103 mg/dL) compared with conventional control (180 to 200 mg/dL).
    The benefit of intensive glycemic control was evident on outcomes such as the occurrence of sepsis, need for dialysis, need for blood transfusion, and development of acute polyneuropathy.
    Intensive insulin therapy was also associated with cost savings compared with conventional insulin therapy in mechanically ventilated patients.
    However, a number of subsequent studies have clearly shown that as blood glucose levels approach normoglycemia, the risks of hypoglycemia, especially severe hypoglycemia, can offset the benefi ts of tight blood glucose control. A follow-up study by Ven den Berghe et al in a medical ICU failed to show a mortality benefit from tight glycemic control, though patients in the intensive control arm experienced less renal injury, faster weaning from ventilation, and earlier discharge from the ICU and hospital. The recent NICE-SUGAR study of aggressive glucose control in the ICU randomized patients to a target blood glucose of 81 to 108 mg/dL (intensive group) or 180 mg/dL or less (control group).12 At study’s end, the groups’ mean blood glucose levels were 115 mg/dL and 144 mg/dL, respectively, while rates of severe hypoglycemia (blood glucose < 40 mg/dL) were 6.8% and 0.5%, respectively. Mortality rates were higher in the intensive therapy group (27.5%) than in the control group (24.9%), driven by severe hypoglycemic events. Notably, blood glucose monitoring in this and other studies was conducted at a frequency of anywhere between 1 and 4 hours. The conclusions of the available data would support, for the time being, a modified glycemic target in critically ill patients, with strict avoidance of severe hypoglycemia.
    The recent consensus statement from the American Association of Clinical Endocrinologists and the American Diabetes Association recommends using insulin therapy if blood glucose levels exceed 180 mg/dL, with target glucose levels less than 180 mg/dL in critically ill patients and less than 140 mg/dL in non–critically ill patients.13 Development and implementation of safer insulin infusion algorithms and more frequent and accurate blood glucose monitoring in this setting should enable us to achieve better glycemic targets with lower risk.
  • Given the concern regarding metformin and the possibility of lactic acidosis, some recommend to discontinue it 48 hours prior to surgery. However, there are very few reported cases of lactic acidosis in the perioperative period, and in general, the association of lactic acidosis with metformin is no different from that of any other oral hypoglycemic agent in the non-surgical setting. Therefore, there is no clinical evidence on which to base this recommendation. If the likelihood of perioperative hypotension and the need for contrast is low, there is probably no reason to stop metformin 48 hours before surgery. For low-risk procedures and those under local anesthesia, metformin can be withheld on the morning of surgery.
    In patients with type 2 diabetes, oral agents pose certain safety risks and should be discontinued prior to surgery. Sulfonylureas may induce hypoglycemia in patients who are placed on NPO (“nothing by mouth”) orders and should be held in patients who are fasting.
    Metformin can induce lactic acidosis if kidney function declines and should be withheld 1 to 2 days before planned surgery if a need for IV contrast is anticipated
    or the procedure could potentially lead to hemodynamic instability and reduced renal perfusion.
    Thiazolidinediones may cause fl uid retention that can complicate the postoperative period; they can be discontinued several days prior to a planned surgery.
    GLP-1 agonists, such as exenatide, can slow gastric motility and potentially delay gastrointestinal recovery after major surgery; they should be held the day of surgery.
    DPP-4 inhibitors (incretin enhancers), such as sitagliptin, do not have signifi cant side effects and, if need be, can be continued. Because incretin therapies act via a glucose-dependent mechanism, they are unlikely to cause hypoglycemia, even in a patient whose oral intake is held or delayed. On the other hand, since their effect is mostly in reducing postprandial glycemia, there may be little need to use them in a patient who is NPO.
    For patients on insulin, there are various options. Options range from most to least physiologic—switch to IV regular insulin, give half to two-thirds of the morning intermediate-acting insulin (neutral protamine Hagedorn or NPH), or give no insulin and no glucose preoperatively and just cover with regular insulin as needed.40 IV insulin is used primarily in an intensive care unit setting (especially for postoperative CABG patients)41 and for patients with diabetic ketoacidosis. The most commonly used regimen is half to two-thirds of the NPH dose depending on the patient’s glucose level.
    There are no specific recommendations from the manufacturers for perioperative management of basal insulin such as insulin glargine and detemir. Basal insulin should be given to these patients, but many physicians opt to decrease the dose, anywhere from 10% to 50%, to avoid hypoglycemia. Hypoglycemia could happen if the patient were given the full insulin dose, did not eat, and had surgery in the late morning or early afternoon. Perioperative management of the patient with diabetes is discussed in more detail in our upcoming Diabetes Management: Glycemic Control in the Hospital module.
    Patients with type 1 diabetes must continue basal insulin replacement preoperatively (0.2 to 0.3 U/kg/day of a long acting insulin). Patients with type 2 diabetes may benefit from basal insulin replacement, as previously noted.
    Supplemental insulin scales are used to correct hyperglycemia regardless of a patient’s oral intake status. They can be individualized based on the estimated total daily insulin dose and require glycemic targets to be established. Fingerstick glucose monitoring should be done every 4 to 6 hours in a patient who is NPO, and supplemental-scale insulin should be used to correct glucose values that exceed target. For supplemental-scale coverage, rapid-acting insulin analogs have a shorter duration of action than human regular insulin and may be given subcutaneously every 4 to 6 hours, whereas regular insulin should not be given more often than every 6 hours to correct hyperglycemia. These differences in action duration should be kept in mind to minimize the potential for insulin stacking.
  • For patients on insulin, there are various options. Options range from most to least physiologic—switch to IV regular insulin, give half to two-thirds of the morning intermediate-acting insulin (neutral protamine Hagedorn or NPH), or give no insulin and no glucose preoperatively and just cover with regular insulin as needed.40 IV insulin is used primarily in an intensive care unit setting (especially for postoperative CABG patients)41 and for patients with diabetic ketoacidosis. The most commonly used regimen is half to two-thirds of the NPH dose depending on the patient’s glucose level.
    There are no specific recommendations from the manufacturers for perioperative management of basal insulin such as insulin glargine and detemir. Basal insulin should be given to these patients, but many physicians opt to decrease the dose, anywhere from 10% to 50%, to avoid hypoglycemia. Hypoglycemia could happen if the patient were given the full insulin dose, did not eat, and had surgery in the late morning or early afternoon. Perioperative management of the patient with diabetes is discussed in more detail in our upcoming Diabetes Management: Glycemic Control in the Hospital module.
    Patients with type 1 diabetes must continue basal insulin replacement preoperatively (0.2 to 0.3 U/kg/day of a long acting insulin). Patients with type 2 diabetes may benefit from basal insulin replacement, as previously noted.
    Supplemental insulin scales are used to correct hyperglycemia regardless of a patient’s oral intake status. They can be individualized based on the estimated total daily insulin dose and require glycemic targets to be established. Fingerstick glucose monitoring should be done every 4 to 6 hours in a patient who is NPO, and supplemental-scale insulin should be used to correct glucose values that exceed target. For supplemental-scale coverage, rapid-acting insulin analogs have a shorter duration of action than human regular insulin and may be given subcutaneously every 4 to 6 hours, whereas regular insulin should not be given more often than every 6 hours to correct hyperglycemia. These differences in action duration should be kept in mind to minimize the potential for insulin stacking.
  • 18 male patients with stable medical condition requiring invasive surgery. Intervention
    group age 44-76 years, mean 65 years; control group age 34-72 years, mean 57 years
    Intervention group: daily dose of 10-15mg prednisolone for 2 months to 3 years
    Control group: daily prednisolone 5-60mg for 2 months to 20 years
    Inclusion criteria: ACTH stimulation test result using cortrosyn with 60-minute cortisol
    level below 20μg/dL (550nmol/L)
    Exclusion criteria: a) primary adrenal insufficiency or pituitary disease, b) non-invasive
    surgery deemed not physiologically stressful, c) 60-min cortisol level above 20μg/dL
    Surgery: invasive surgery under either local, spinal, epidural, or general anaesthesia.
    Length of surgery between 30 minutes to 290 minutes
    Interventions Intervention group: intravenous injection of 100mg cortisol 1 hour before surgical procedure,
    25mg every 6 hours for 2 days and every 12 hours for 1 day
    Control group: identical regime of intravenous injection of normal saline
    18 male and 2 female organ transplant recipients with clinically significant drug-induced
    gingival overgrowth in at least 2 quadrants requiring surgical intervention. Age 21-71
    years, mean 38.9 years
    Daily prednisolone dose of 5-15mg and cyclosporin for at least 6 months
    Exclusion criteria: not specified
    Surgery: standardized gingivectomy in one quadrant of themouth under local anaesthetic
    of lignocaine 2% with 1:80,000 adrenaline
    Interventions Intervention: intravenous hydrocortisone hemisuccinate 100mg immediately before
    surgery
    Control: matching placebo
  • A normal functioning adrenal gland produces approximately 5.7 mg (=15.7 μmol) cortisol per square meter of body surface area [11]. This means that a male with a length of 1.80 m and 75 kg produces approximately 30 μmol of cortisol per day. The oral supplementation in a patient without any endogenous cortisol production would be twice the endogenous production. This higher dose is needed to overcome biological availability and the first-pass metabolism of the liver. In reaction to physical stress (sepsis, burn wounds, major operations and critical illness) the endogenous cortisol production can increase 5–6 times [12,13]. The perioperative
    supplementation of glucocorticosteroids was based on three assumptions: (a) exogenous glucocorticosteroids suppress the HPA-axis; (b) a maximally stimulated adrenal gland produces the equivalent of 200–300 mg of cortisol, and; (c) therefore patients with suppressed HPA-axis need extreme doses of glucocorticosteroids.
    Abbreviations: CC, case-control; ND, not determined; NR, not reported; P, prospective; R, retrospective; RA, rheumatoid arthritis; RCT, randomized controlled trial.
    Conclusions: Patients receiving therapeutic doses of corticosteroids who undergo a surgical procedure do not routinely require stress doses of corticosteroids so long as they continue to receive their usual daily dose of corticosteroid.
    Adrenal function testing is not required in these patients because the test is overly sensitive and does not predict which patient will develop an adrenal crisis. Patients receiving physiologic replacement doses of corticosteroids owing to primary disease of the hypothalamicpituitary- adrenal axis, however, require supplemental doses of corticosteroids in the perioperative period.
  • Cortisol > 20 mcg/dL – descarta insuficiencia suprarrenal
    Cortisol 8AM < 3 mcg/dL – confirmal insuficiencia suprarrenal
    Cosintropin – cortisol > 20 mcg/dL – descarta insuficiencia suprarenal
    - si a pesar sigue la sospecha entonces  hipoglucemia inducida por insulina; metirapona; CRH
    Cosintropin < 20 mcg/dL – confirma insuficiencia suprarrenal.
  • Less commonly used today; refractory depression
    Accumulation of Biogenic Amines in CNS and autonomic NS
    Two types of MAO reactions
    Type 1 (excitatory):
    serotonin syndrome
    Type 2 (depressive):
    inhibits hepatic microsomal enzymes,
    leads to accumulation of narcotic
    Indirect Sympathomimetics (ephedrine)
    massive release of stored NE  severe HTN
  • In summary, most neuropsychiatric medications are continued preoperatively, although consultation with the patient’s psychiatrist or neurologist is advisable.
  • St Johns wort - Some of the drugs that may be affected include indinavir sulfate, ethinyl estradiol, cyclosporin, alfentanil, midazolam hydrochloride, lidocaine, calcium channel blockers, serotonin receptor antagonists, and NSAIDs.
    Echinacea affects cell-mediated immunity and has also been associated with allergic reactions. Although there is little research on the effects of these drugs in the perioperative period and the time period that these potential adverse effects may last after the drug is stopped is unknown, it is usually recommended that all herbal medications be discontinued at least 1 week before surgery.
    In summary herbal medications should be discontinued 1 to 2 weeks before surgery to avoid potentially adverse interactions.
  • CAVEAT MEDICUS!
    No FDA regulation on content of herbs
    Food supplements
    Natural = Good, Artificial = Bad???
    Actual doses widely vary
    50 commercial ginseng preps in 11 countries
    44: 1.9 to 9.0%; 6 had none!
    Swedish athlete tested + hi dose ephedrine while taking only ginseng prep
    Stop 7d prior to surgery; consider taper of valerian +/- BZD coverage
  • Farmacología perioperatoria

    1. 1. Farmacología Perioperatoria Dr. Moises Auron, FAAP, FACPDr. Moises Auron, FAAP, FACP Staff, Departamento de Medicina Hospitalaria yStaff, Departamento de Medicina Hospitalaria y Sección de Medicina Hospitalaria PediátricaSección de Medicina Hospitalaria Pediátrica Nov – 27 – 2010
    2. 2. Conflicto de intereses • Ninguno
    3. 3. Objetivos • Revisar los principios generales para continuar ó descontinuar medicamentos en la etapa perioperatoria. • Discutir evidencia y controversias alrededor del manejo de medicamentos en la etapa peri-operatoria • Delinear una guia practica para el manejo perioperatorio de medicamentos. • Se discutirán los medicamentos más utilizados y de mayor controversia.
    4. 4. Justificación • Incremento en la complejidad quirúrgica - Incremento en la población geriátrica • Falta de entrenamiento formal en Medicina Perioperatoria • Cese ó inicio involuntario de medicamentos • EUA – requerimiento federal (Joint Commission on Accreditation of Healthcare Organizations - JCAHO) - Objetivo Nacional de Seguridad del Paciente (NPSG) - #3: Incrementar la seguridad en el manejo de medicamentos - #8: Reconciliación de medicamentos - precisa y completa en todos los ámbitos de transición médica. http://www.jointcommission.org/patientsafety/nationalpatientsafetygoals
    5. 5. Evidencia de las recomendaciones • No existen estudios aleatorizados • Consenso de expertos • Entendimiento de la farmacología - Farmacocinética - Efecto terapéutico - Interacción con anestésicos • Consideraciones teóricas (multivitamínicos) • Reporte de casos Whinney C. CCJM. Nov 2009; 76(Suppl 4): S126-S132.
    6. 6. Consulta Perioperatoria • Historia clínica completa - Entender el riesgo perioperatorio • Historia farmacológica del paciente: - Medicamentos de prescripción - Medicamentos no prescritos (OTC) - Vitaminas - Suplementos nutricionales/herbales - Alcohol/tabaco/drogas Clay BJ. J Hosp Med. 2008 Nov-Dec;3(6):465-72.
    7. 7. Principios Generales • Respuesta de estrés a la cirugía y cambios hemodinámicos de la anestesia: - ↑ tono simpático - ↑ vasopresina - ↑ cortisol - ↑ eje renina-angiotensina-aldosterona - ↑ Producción local de prostaglandinas vasodilatadoras
    8. 8. Principios Generales • Disminución de absorción gastrointestinal - Cambios en en flujo sanguíneo esplácnico - Edema transmural del intestino - Atrofia de las vellosidades - Hipomotilidad • Íleo, opioides, anticolinérgicos, alteraciones electrolíticas Whinney C. CCJM. Nov 2009; 76(Suppl 4): S126-S132. Pass SE. Am J Health Syst Pharm. 2004 May 1;61(9):899-912.
    9. 9. Principios Generales • Descontinuación - Efectos de rebote - Síndromes de supresión - Empeoramiento clínico intra-operatorio • Continuación - Hemorragia - Hipoglucemia - Interacción con anestésicos - Complicaciones post- operatorias • O.R. 2.7 (95% CI, 1.76–4.04) Pass SE. Am J Health Syst Pharm. 2004 May 1;61(9):899-912. Kennedy JM. Br J Clin Pharmacol. 2000 Apr;49(4):353-62.
    10. 10. Principios Generales • La descontinuación abrupta de medicamentos puede llevar a fenómenos de supresión: - ISRS (SSRI) - Beta-bloqueadores - Clonidina - Benzodiazepinas - Estatinas - Corticosteroides. Papadopoulos S. Orthopedics 2006; 29:413-17. Marik PE. Arch Surg. 2008;143(12):1222-1226.
    11. 11. Principios Generales Arch Intern Med. 2006;166:2525-2531.
    12. 12. Principios Generales • Continuar medicamentos con potencial de rebote • Descontinuar los que: - Incrementan riesgo quirúrgico - No esenciales para la calidad de vida • Usar el razonamiento clínico Whinney C. CCJM. Nov 2009; 76(Suppl 4): S126-S132.
    13. 13. Paciente geriátrico Auron-Gomez M. Clin Geriatr Med. 2008; 24: 701–719
    14. 14. Paciente geriátrico Singh A. Current Opinion in Anaesthesiology 2010; 23:449–454 ↓ distensibilidad Vascular Hipertrofia ventricular ↑ sensibilidad a la precarga+ ↓ reflejos baroceptores ↓ respuesta a hipovolemia ↓ volúmen expiratorio forzado ↓ de la capacidad de cierre alveolar shunt fisiológico + Atelectasias Hypoxemia Neumonía
    15. 15. Paciente geriátrico Rivera R. Anesthesiology 2009; 110:1176–81.
    16. 16. Paciente obeso mórbido ↑ gasto cardiaco ↑ peso corporal magro ↑ masa adiposa ↑ volúmen extracelular Lemmens HJM. Current Opinion in Anaesthesiology 2010, 23:485–491. Janmahasatian S, Clin Pharmacokinet 2005; 44:1051–1065.
    17. 17. Paciente obeso mórbido Lemmens HJM. Current Opinion in Anaesthesiology 2010, 23:485–491. Janmahasatian S, Clin Pharmacokinet 2005; 44:1051–1065.
    18. 18. Caso 1 Hombre de 75 años con masa renal izquierda. Historia de hipertensión arterial y enfermedad coronaria (stent metálico en ACD 3 meses atrás). Toma Atenolol 25 mg/d; Clopidogrel 70 mg/d y Aspirina 81 mg/d Programado para hemi-nefrectomía robótica. ¿ Cual es su recomendación para el manejo peri-operatorio de anti- plaquetarios? a) Continuar el clopidogrel y aspirina b) No administrar el clopidogrel ni la aspirina el día de la cirugía c) Suspender el clopidogrel 5 días antes de la cirugía y continuar aspirina d) Suspender el clopidogrel y la aspirina 7 días antes de la cirugía e) Suspender la aspirina 7 días antes de la cirugía y continuar clopidogrel
    19. 19. Aspirina (ASA) • Inhibición irreversible de ciclooxigenasa (COX) • 7-10 días para regeneración plaquetaria • Uso perioperatorio ↓ morbilidad cardiovascular • El cese > 5 días  riesgo de ECV y SCA • Decisión de continuar vs. descontinuar depende del riesgo hemorrágico vs. morbilidad cardiovascular perioperatoria. - E.g. Neurocirugía; cirugía de próstata, etc. • Reiniciar 24 horas después de la cirugía (ACCP 2008) Oscarsson A. Br J Anaesth. 2010 Mar;104(3):305-12. O’Riordan JM. Arch Surg. 2009;144(1):69-76. 2008 ACCP Guidelines on Antithrombotic Therapy. Chest. 2008 Jun;133(6 Suppl):299S-339S.
    20. 20. Stents intracoronarios 2007 ACC/AHA Perioperative Task Force. Circulation. 2009;120:e169-e276. 2008 ACCP Guidelines on Antithrombotic Therapy. Chest. 2008 Jun;133(6 Suppl):299S-339S.
    21. 21. Otros antiplaquetarios • Tienopiridinas - Inhibición irreversible de la agregación plaquetaria inducida por ADP • Descontinuar: - Clopidogrel – 5 días - Prasugrel – 7 días - Ticlopidina – 10-14 días • Reiniciar a la brevedad. • En pacientes con stents, continuar ASA Cohn S. Perioperative Medicine. Mc Graw Hill. 2007. Pp 36-49. Jaffer A. CCJM. 2009; 76(Suppl 4): S37-S44.
    22. 22. AINES • Inhibición reversible de COX-1  ↓ TXA2  ↓ agregación plaquetaria - Nefrotoxicidad - Incrementan riesgo de sangrado 1.5x a 2x • COX-2 (celecoxib) – efecto mínimo en función plaquetaria - Nefrotoxicidad - Efectos cardiovasculares deletéreos - ↓ opioides post-operatorios • AINES no acetilados (salsalato) –no tienen efecto antiplaquetario Straube S. Acta Anaesthesiol Scand. 2005;49:601-613. O’Riordan JM. Arch Surg. 2009;144(1):69-76.
    23. 23. AINES • Se sugiere suspenderlos debido a su nefrotoxicidad y riesgo de hemorragia gastrointestinal. • Efecto antiplaquetario depende de su vida media - Análisis de función plaquetaria (PFA-100) – normalización in-vitro 24 horas después de suspender ibuprofeno. • Descontinuar 3 días antes de la cirugía - ibuprofen puede usarse hasta 24 horas antes. Goldenberg NA. Ann Intern Med 2005 Apr 5;142(7):506-9.
    24. 24. Guías ACCP 2008 2008 ACCP Guidelines on Antithrombotic Therapy. Chest. 2008 Jun;133(6 Suppl):299S-339S. Jaffer A. CCJM. 2009; 76(Suppl 4): S37-S44.
    25. 25. Calificación CHADS2 Snow V. Ann Intern Med 2003; 139:1009–1017. Jaffer A. CCJM. 2009; 76(Suppl 4): S37-S44.
    26. 26. Guias ACCP 2008 • Trancisión a heparina de bajo peso molecular ó heparina no fraccionada: - Riesgo tromboembólico moderado-alto. • Dosis profiláctica de heparina de bajo peso molecular: - Riesgo tromboembólico bajo. 2008 ACCP Guidelines on Antithrombotic Therapy. Chest. 2008 Jun;133(6 Suppl):299S-339S.
    27. 27. Trancisión de anticoagulantes • Vida media x 4 = tiempo de suspensión - Warfarina ~ 5 días - Iniciar UFH o LMWH 36 horas después de última dosis de warfarina - Ultima dosis de LMWH 24 horas antes de cirugía - Detener UFH 6 horas antes de cirugía 2008 ACCP Guidelines on Antithrombotic Therapy. Chest. 2008 Jun;133(6 Suppl):299S- 339S. Levy JH. Anesthesiology 2010; 113(3):726 – 45.
    28. 28. Caso 2 Mujer de 90 años con enfermedad vascular periférica y fibrilación auricular. Medicamentos: warfarina 5 mg/d; aspirina 325 mg/d; diltiazem ER 180 mg/d. Programada para cirugía de catarata. ¿Cual es su recomendación para el manejo perioperatorio de warfarina y aspirina? a) Continuar warfarina y aspirina b) Suspender aspirina 7 días antes y warfarina 5 días antes c) Trancisión de warfarina a heparina de bajo peso molecular d) Cancelar cirugía debido a la edad de la paciente e) Suspender warfarina 5 días antes y continuar aspirina
    29. 29. Continuar antiplaquetarios y anticoagulantes en cirugía de catarata • Estudio prospectivo de cohortes (N = 19,283)  no diferencia significativa en complicaciones locales (hemorragia) ó sistémicas (TIA, SCA) en pacientes que continuaron vs. detuvieron ASA y warfarina. • Estudio retrospectivo (N = 48,862) – Auditoria de base de datos nacional de catarata –uso de warfarina y clopidogrel  no se asoció con incremento sigificativo de complicaciones anestésicas o hemorrágicas que comprometan la visión Katz J. Ophthalmology 2003 Sep;110(9):1784-8. Benzimra JD. Eye. 2009;23(1):10-16.
    30. 30. Guías ACCP 2008 • Continuar antagonistas de vitamina K - Procedimientos dentales - con uso de agentes pro- hemostáticos orales (epsilon-aminocapróico) • Higiene dental, extracciones simples, prótesis, restauraciones, endodoncia, periodoncia - Procedimientos dermatológicos menores • Mohs; excisiones simples - Cirugía de catarata y trabeculectomía 2008 ACCP Guidelines on Antithrombotic Therapy. Chest. 2008 Jun;133(6 Suppl):299S-339S. Jaffer A. CCJM. 2009; 76(Suppl 4): S37-S44.
    31. 31. Nuevos anticoagulantes Levy JH. Anesthesiology 2010; 113(3):726 – 45.
    32. 32. Nuevos anticoagulantes Suspender x 4 VM = ~ 2 días Levy JH. Anesthesiology 2010; 113(3):726 – 45.
    33. 33. Caso 3 Hombre de 65 años con hiperlipidemia, hipertensión y diverticulosis severa. Medicamentos: rosuvastatina y clortalidona. Programado para hemicolectomía izquierda en 2 semanas. El paciente sube 2 pisos de escaleras sin problemas. ¿Que recomendación le daría al paciente? a) Suspender la clortalidona el día de la cirugía b) Suspender ambos medicamentos el día de la cirugía c) Continuar la rosuvastatina y la clortalidona d) Iniciar atenolol ahora y ajustar dosis a un pulso de 60-70x’
    34. 34. Diuréticos • Se recomienda descontinuar el día de la cirugía - Hipovolemia - Trastornos electrolíticos • Hipokalemia • Hiponatremia • Hipo/Hipercalcemia • Individualizar en pacientes con insuficiencia cardiaca congestiva Whinney C. CCJM. Nov 2009; 76(Suppl 4): S126-S132.
    35. 35. Inhibidores del eje RAA IECA BRA Antagonistas de aldosterona • Eplerenona, espironolactona Bloqueador directo de renina • Aliskiren Inhibición del efecto vasoconstrictor de Angiotensina II ↓ Aldosterona ↑ Agentes vasodilatadores (Bradykinina, NO, prostaciclinas) ANESTESIA + Fyhrquist F. J Intern Med. 2008 Sep;264(3):224-36. Comfere T. Anesth Analg. 2005;100:636-644. ↑ hipotensión post-inducción ↑ Uso de vasoconstrictores (agonistas adrenérgicos, vasopresina) “Pooling” de sangre venosa ↓ Gasto cardíaco
    36. 36. Inhibidores del eje RAA RR de hipotensión tratada con vasopresores post-inducción Rosenman DJ. J Hosp Med. 2008 Jul;3(4):319-25.
    37. 37. Rosenman DJ. J Hosp Med. 2008 Jul;3(4):319-25. RR de infarto miocárdico post-operatorio Inhibidores del eje RAA
    38. 38. • Estudio retrospectivo (1996 - 2008) • N = 10,023 (3,052 IECA vs. control – analisis de propensión) • IECA preoperatorio  complicaciones postoperatorias - Mortalidad (OR: 2.83, 95% CI: 1.03 to 7.8; P = 0.04) - Nefrotoxicidad (OR: 1.7, 95% CI: 1.22 to 2.38; P = 0.0002 - Fibrilacion auricular (OR: 1.33, 95% CI: 1.17 to 1.51; P = 0.0001) - Inotropicos (OR: 1.17, 95% CI: 1.07 to 1.29; P = 0.0001). • Mortalidad total: 1%. - IECA: x 2 (1.3% vs. 0.7%; OR: 2.00, 95% CI: 1.17- 3.42; P = 0.013). J Am Coll Cardiol 2009;54:1778–84.
    39. 39. IRAA - Recomendación • Descontinuar IECA – una dosis • Descontinuar BRA – 24 h • Aliskiren – VM ~ 24 h  ~ 3 días? • Espironolactona – una dosis • Eplerenona – una dosis Whinney C. CCJM. Nov 2009; 76(Suppl 4): S126-S132. Saber W. CCJM. Mar 2006;73(Suppl 1):S82-7. Auron M. enviado a publicación (Postgrad Med J)
    40. 40. Fisiopatología de isquemia perioperatoria ↑↑ tono simpáticotono simpático ↑↑ catecolaminas séricascatecolaminas séricas ↑↑ cortisolcortisol ↑↑ VOVO22 miocárdicomiocárdico Estado inflamatorioEstado inflamatorio - TNFTNF αα - Prot C reactivaProt C reactiva - IL-1 and IL-6IL-1 and IL-6 - Ac. grasos libresAc. grasos libres ↑↑ Función plaquetariaFunción plaquetaria Disfunción endotelialDisfunción endotelial • AnestesiaAnestesia • Compartimentalizacion de líquidosCompartimentalizacion de líquidos • AnemiaAnemia • DolorDolor • ↑↑ Demanda metabólicaDemanda metabólica ++ ++ ↑↑ fuerza tensional en la placafuerza tensional en la placa de ateromade ateroma Ruptura de la placaRuptura de la placa ↓↓OO22 tisulartisular IAM No–QIAM No–Q
    41. 41. Betabloqueadores Chopra V. JAMA. Feb 10 2010; 303(6): 551-2.
    42. 42. Devereaux PJ, et al. Lancet 2008; 371: 1839 – 47. ECV Muerte Resultado 1˚ IAM HR 0.84, 95%CI 0.70–0.99 HR 0.73, 95%CI 0.60–0.89 HR 2.17, 95%CI 1.26–3.74 HR 1.33, 95%CI 1.03-1.74 N = 8351 - Metoprolol 4174 - Placebo 4177 Resultado primario – compuesto de mortalidad CV, IAM no fatal, paro cardiaco no fatal Succinato de metoprolol 200 mg/d
    43. 43. Betabloqueadores Perioperatorios Lindenauer PK. N Engl J Med 2005;353: 349-61. RCRI Diabetes Enfermedad coronaria Enfermedad cerebrovascular Insuficiencia cardiaca Insuficiencia renal (cre > 2)
    44. 44. • Timing of Pre-Operative Beta-Blocker TreatmentTiming of Pre-Operative Beta-Blocker Treatment in Vascular Surgery Patients. Influence on Post-in Vascular Surgery Patients. Influence on Post- Operative OutcomeOperative Outcome • N = 940 pacientes de cirugía vascularN = 940 pacientes de cirugía vascular • Eventos cardiacos a 30 días:Eventos cardiacos a 30 días: - 1-4 semanas - O.R. 0.46, 95% CI: 0.27 to 0.761-4 semanas - O.R. 0.46, 95% CI: 0.27 to 0.76 - > 4 semanas - O.R. 0.48, 95% CI: 0.29 to 0.79> 4 semanas - O.R. 0.48, 95% CI: 0.29 to 0.79 • Mortalidad a largo plazo:Mortalidad a largo plazo: - 1- 4 semanas – H.R. 0.52, 95% CI: 0.21 to1- 4 semanas – H.R. 0.52, 95% CI: 0.21 to 0.670.67 - > 4 semanas – H.R. 0.50, 95% CI: 0.25 to 0.71> 4 semanas – H.R. 0.50, 95% CI: 0.25 to 0.71 Flu WJ. J Am Coll Cardiol, 2010; 56:1922-1929, Betabloqueadores Perioperatorios
    45. 45. BetabloqueadoresBetabloqueadores • Clase I - continuar en los pacientes con uso activo • Clase IIa - Probablemente recomendados en cirugía vascular en pacientes de alto riesgo (enfermedad coronaria; prueba de esfuerzo positiva) - Razonable en pacientes con enfermedad coronaria o mas de 1 factor de riesgo CV. • Clase IIb - Incierto en ausencia de enfermedad coronaria - Incierto en ausencia de factores de riesgo • Class III - No usar en pacientes con contraindicaciones. - Peligroso iniciar dosis elevadas sin incremento paulatino en pacientes que no usaban BB. Circulation 2009;120;e169-e276;
    46. 46. Hipolipemiantes • Estatinas - Evidencia favorable (↓ complicaciones cardiovasculares) • DECREASE IV - Disminución de tromboembolismo venoso - Se sugiere su continuación • Colestiramina - Disminuye absorción de otros fármacos • Fibratos y Niacina - Rabdomiolisis - No ofrecen beneficios perioperatorios 2007 ACC/AHA Perioperative Task Force. Circulation. 2009;120:e169-e276. Dunkelgrun M. Ann Surg. 2009;249:921-926. Glynn RJ. N Engl J Med. 2009;360:1851-1861. Descontinuar
    47. 47. Otros medicamentos cardiovasculares • Clonidina - Propiedades ansiolíticas - Efecto de hipertensión de rebote - Se sugiere su continuación perioperatoria. • α bloqueadores - Usados en hipertrofia prostática - Tamsulosina – descontinuar antes de la cirugía de catarata • Síndrome de iris flácido intraoperatorio - Se sugiere descontinuar pre-operatoriamente • Calcioantagonistas - Se sugiere su continuación. • Anti-anginosos y antiarrítmicos - Se sugiere su continuación. Abdel-Aziz S. Curr Opin Ophthalm. 2009; 20:37–41 Wallace AW. Anesthesiology. 2004;101:284-293. Bell CM. JAMA. 2009;301:1991-1996. Wijeysundera DN. Anesth Analg. 2003;97:634-641.
    48. 48. Caso 4 Hombre de 25 años con DM tipo 1, ICC (EF 30%), IRCT candidato a transplante renal. Medicamentos – bomba de infusión de insulina, atorvastatina, carvedilol, lisinopril. ¿Qué recomendación sugiere para el manejo pre-operatorio de la insulina? a) Suspender la bomba y convertir a insulina de larga duración b) Continuar infusión basal de insulina c) Iniciar infusión intravenosa de insulina y glucosa (pinza euglucémica) d) Suspender la bomba e iniciar escala de insulina subcutánea ajustada a glucosa capilar
    49. 49. Objetivos del control glicémico • Evitar hipo- e hiperglicemia • Mantener equilibiro hidroelectrolítico • Prevenir cetoacidosis • Mantener control glicémico estricto - UTI: > 110 mg/dL < 180 mg/dL - No UTI: > 100 mg/dL < 140 mg/dL Meneghini LF. CCJM. Nov 2009; 76 (Suppl 4): S53-S59
    50. 50. Diabetes Care. Jun 2009; 32(6):1119-1131.
    51. 51. Manejo pre-operatorio de DM • Suspender hipoglucemiantes orales en la mañana de la cirugía - Clorpropamida (~2 días antes) - Metformin  continuar el día previo - Tiazolidinedionas (pioglitazona) - agonistas GLP-1 (exenatida) - inhibidores de DPP-4 (sitagliptina) Meneghini LF. CCJM. Nov 2009; 76 (Suppl 4): S53-S59 Duncan AI. Anesth Analg. 2007;104:42-50. Salpeter S. Cochrane Database Syst Rev. 2002:CD002967.
    52. 52. • Insulina - Día previo  mismo régimen - Día de la cirugía: • No usar insulina de acción rápida • Insulina de larga duración: 50% dosis • Bomba de infusión  continuar tasa basal Meneghini LF. CCJM. Nov 2009; 76 (Suppl 4): S53-S59 Duncan AI. Anesth Analg. 2007;104:42-50. Salpeter S. Cochrane Database Syst Rev. 2002:CD002967. Manejo pre-operatorio de DM
    53. 53. • Insulina 70/30 - Componente de larga duración (NPH): 50% - 50 u  70% = 35 u  Administrar la mitad ~ 17 u Manejo pre-operatorio de DM Meneghini LF. CCJM. Nov 2009; 76 (Suppl 4): S53-S59 Duncan AI. Anesth Analg. 2007;104:42-50. Salpeter S. Cochrane Database Syst Rev. 2002:CD002967.
    54. 54. Caso 5 Mujer de 80 años con Polimialgia reumática admitida con colelitiasis. Medicamentos: Prednisona 5 mg diarios. Programada para colecistectomía laparoscópica. Cual es su recomendación para el manejo perioperatorio de esteroides? a) Continuar la misma dosis de prednisona b) Administrar 15 mg de prednisona c) Omitir la dosis de prednisona d) Administrar hidrocortisona 100 mg i.v. en inducción anestésica
    55. 55. Esteroides • 2 estudios aleatorizados con placebo • Pacientes en dosis basal de esteroides Yong SL. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD005367. No es posible refutar ó apoyar la práctica de suplementación perioperatoria de esteroides.
    56. 56. Marik PE. Arch Surg. 2008;143(12):1222-1226 de Lange DW. Eur J Int Med. 2008; 19: 461–467
    57. 57. Esteroides Supresión Del eje HH Estrés Qx menor (hernia) Estrés Qx moderado (reemplazo articular) Estrés Qx mayor (Revasc. coronaria) No PDN < 5 mg/dPDN < 5 mg/d Esteroides < 3 sEsteroides < 3 s Cosintropin -voCosintropin -vo Dosis diariaDosis diaria No suplementarNo suplementar Dosis diariaDosis diaria No suplementarNo suplementar Dosis diariaDosis diaria No suplementarNo suplementar Documentada ó sospechosa PDN > 20 mg/d > 3s Cushingoide Cosintropin +vo Dosis diaria No suplementar Hidrocortisona 50 mg iv (inducción) 25 mg iv q8h x 24h-48h Hidrocortisona 100 mg iv (inducción) 50 mg iv q8h x 24h 25 mg iv q8h x 24-48h Incierto PDN 5-10 mgPDN 5-10 mg >> 3s3s Dosis diariaDosis diaria No suplementarNo suplementar Cosintropin +Cosintropin + HidrocortisonaHidrocortisona 50 mg iv (inducción)50 mg iv (inducción) 25 mg iv q8h x 24h-48h25 mg iv q8h x 24h-48h HidrocortisonaHidrocortisona 100 mg iv (inducción)100 mg iv (inducción) 50 mg iv q8h x 24h50 mg iv q8h x 24h 25 mg iv q8h x 24-48h25 mg iv q8h x 24-48h Shaw M. CCJM. 2002;69(1):9-11 Schiff RL. Med Clin North Am. 2003 Jan;87(1):175-92. Cohn SL. Perioperative Medicine. McGraw Hill. 2006. Pp 158-163.
    58. 58. Caso 6 Hombre de 70 años con EPOC. Nunca intubado. Hospitalizado 1 año atrás. Usa salmeterol con fluticasona, tiotropio, albuterol prn con espaciador y montelukast. El paciente se encuentra asintomático. Programado para recambio articular de cadera. ¿Qué recomendacion dará para el manejo médico del EPOC el día de la cirugía? a) No usar inhaladores. Administrar hidrocortisona i.v. b) Administrar prednisona 60 mg/d empezando 48 h antes c) Continuar todos los inhaladores d) Realizar espirometría y ajustar los inhaladores. e) Suspender el montelukast, e iniciar teofilina.
    59. 59. EPOC / Asma Yamakage M. J Anesth. 2008; 22:412–428
    60. 60. EPOC / Asma • Continuar - Broncodilatadores - Esteroide inhalado - Montelukast • Optimizar los síntomas - Antibióticos (esputo espeso) - Esteroides orales (iniciar 5 días antes) • Suspender teofilina (disrritmias) Woods BD. Br J Anaesth 2009; 103 (Suppl. 1): i57–i65. Yamakage M. J Anesth. 2008; 22:412–428 Silvanus MT. Anesthesiology 2004; 100: 1052–7
    61. 61. Caso 7 Mujer de 50 años con enfermedad bipolar y esquizofrenia paranoide. Sus medicamentos incluyen carbonato de Litio, ácido valpróico, olanzapina y escitalopram. Programada para mastectomía para cancer de mama triple negativo. ¿Cuál es su recomendación para el manejo de los psicofármacos? a) Suspender todos el día de la cirugía b) Continuar ácido valpróico y Litio exclusivamente c) Continuar olanzapina y escitalopram exclusivamente d) Suspender olanzapina e) Continuar todos
    62. 62. Medicamentos Neuropsiquiátricos • Inhibidores selectivos de la recaptura de serotonina: - Potencial efecto antiplaquetario - Su suspensión puede causar supresión • Se continúan perioperatoriamente. - En ciertos procedimientos (neurocirugía) puede considerarse su suspensión – discutir con Psiquiatría y suspender gradualmente. Huyse FJ. Psychosomatics 2006; 47:8–22 Weinrieb RM. Expert Opin Drug Saf. 2005;4:337-344. Movig KL. Arch Intern Med. 2003;163:2354-2358. Michelson D. Br J Psychiatry. 2000;176:363-368.
    63. 63. • Antidepresivos tricíclicos: - inhiben la recaptura de norepinefrina y serotonina ∀ ↑ teorético de disrrítmias • Suspensión abrupta  Efecto colinérgico • Se continúan perioperatoriamente. Medicamentos Neuropsiquiátricos Huyse FJ. Psychosomatics 2006; 47:8–22 Cohn SL. Perioperative Medicine. McGraw Hill. 2006. Pp 36-49. Wolfe RM. Am Fam Physician. 1997;56:455-462. Kroenke K. South Med J. 1998;91:358-364.
    64. 64. • Benzodiazepinas  continuar • Antipsicóticos  continuar - Documentar ECG (QTc) • IMAO  suspender 2 semanas antes - Riesgo de HTN con simpatomiméticos - Síndrome serotoninérgico - Evitar meperidina, tiramina - Usar simpatomiméticos directos (fenilefrina) Medicamentos Neuropsiquiátricos Huyse FJ. Psychosomatics 2006; 47:8–22 Cohn SL. Perioperative Medicine. McGraw Hill. 2006. Pp 36-49. Noble WH. Can J Anaesth. 1992;39:1061-1066.
    65. 65. • Litio  continuar - Monitorizar estado hidroelectrolítico (Diabetes insípida nefrogénica) • Antiepilepticos  continuar - Monitorizar niveles séricos - Considerar uso intravenoso • Antiparkinsonianos  continuar - Suspensión abrupta  sx neuroléptico maligno - Consulta a Neurología Medicamentos Neuropsiquiátricos Huyse FJ. Psychosomatics 2006; 47:8–22. Cohn SL. Perioperative Medicine. McGraw Hill. 2006. Pp 36-49. Fujii T. Surg Today. 2009;39(9):807-810. Gálvez-Jiménez N. Neurol Clin. 2004;22(2):367-377. Gray EJ. J Oral Maxillofac Surg. 1996;54:909-912.
    66. 66. Caso 8 Mujer de 50 años con glioblastoma multiforme. Medicamentos: Dexametasona, Levetiracetam, Ginseng, ajo, Gingko- biloba. Programada para craniotomía y resección del tumor en 2 semanas. ¿Cuál es su recomendación para el manejo de medicamentos? a) Continuar todos los medicamentos b) Suspender todos los medicamentos el día de la cirugía c) Suspender el Levetiracetam el día de la cirugía d) Suspender el Ginseng y Gingko-biloba el día de la cirugía e) Suspender el ajo, Gingseng y Ginkgo-biloba ahora
    67. 67. Hierbas y suplementos • Usados por 33% de pacientes quirúrgicos • Sus complicaciones incluyen: - IAM, ECV, hemorragia - Potenciación de los anestésicos - Refracteridad a los anestésicos - Interacciones farmacológicas Ang-Lee MK. JAMA. 2001;286:208-216. Kaye AD. Anesthesiology Clin N Am 2004; 22:125–139. Rowe DJ. Aesthetic Surg J 2009;29:150–157.
    68. 68. Hierbas y suplementos Ginseng Hypoglucemia Inhibe agregación plaquetaria (irreversible) ↑ PT-PTT en animales ↑ Efecto anticoagulante de warfarina Efedra (ma huang) IAM, ECV Depleta depósitos endógenos de catecolaminas  Inestabilidad hemodinámica intraoperatoria Interacción fatal com IMAOs Ajo Inhibe agregación plaquetaria (irreversible) ↑ fibrinolisis  ↑ riesgo de hemorragia Actividad hipotensora errática. Gingko-biloba Inhibe FAP (Factor activador de plaquetas)  ↑ riesgo de hemorragia Ang-Lee MK. JAMA. 2001;286:208-216. Kaye AD. Anesthesiology Clin N Am 2004; 22:125–139 Rowe DJ. Aesthetic Surg J 2009;29:150–157.
    69. 69. Hierbas y suplementos Kava kava Sedación, ansiolysis ↑ Efecto sedante de anestésicos Potencial adictivo  supresión St. John’s Wort (hierba de San Juan) Múltiples interacciones farmacológicas  inducción del sistema microsomal (P450) Echinacea Activación de la inmunidad celular Reacciones alérgicas; inmunosupresión Potencía barbitúricos Valeriana ↑ Efecto sedante de la anestesia Supresión; refractareidad a la anestesia Ang-Lee MK. JAMA. 2001;286:208-216. Kaye AD. Anesthesiology Clin N Am 2004; 22:125–139 Rowe DJ. Aesthetic Surg J 2009;29:150–157.
    70. 70. • Otros: camomila (manzanilla) – anticoagulante • Otros recursos: - www.nccam.nih.gov - (Centro Nacional del Medicina Alternativa y Complementaria) - www.fda.gov/consumer (Administración de Drogas y Alimentos de EUA) - www.herbmed.org (Fundación de Medicina Alternativa) Hierbas y suplementos Kaye AD. Anesthesiology Clin N Am 2004; 22:125–139. Rowe DJ. Aesthetic Surg J 2009;29:150–157.
    71. 71. ¡Muchas gracias!¡Muchas gracias!

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