Pekka Talke

The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery.

UNLABELLEDnWe tested dexmedetomidine, an alpha(2) agonist that decreases heart rate, blood pressure, and plasma norepinephrine concentration, for its ability to attenuate stress responses during emergence from anesthesia after major vascular operations. Patients scheduled for vascular surgery received either dexmedetomidine (n = 22) or placebo (n = 19) IV beginning 20 min before the induction of anesthesia and continuing until 48 h after the end of surgery. All patients received standardized anesthesia. Heart rate and arterial blood pressure were kept within predetermined limits by varying anesthetic level and using vasoactive medications. Heart rate, arterial blood pressure, and inhaled anesthetic concentration were monitored continuously; additional measurements included plasma and urine catecholamines. During emergence from anesthesia, heart rate was slower with dexmedetomidine (73 +/- 11 bpm) than placebo (83 +/- 20 bpm) (P = 0.006), and the percentage of time the heart rate was within the predetermined hemodynamic limits was more frequent with dexmedetomidine (P < 0.05). Plasma norepinephrine levels increased only in the placebo group and were significantly lower for the dexmedetomidine group during the immediate postoperative period (P = 0.0002). We conclude that dexmedetomidine attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia.nnnIMPLICATIONSnThe alpha(2) agonist, dexmedetomidine, attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia in vascular surgery patients.

Dexmedetomidine Does Not Alter the Sweating Threshold, But Comparably and Linearly Decreases the Vasoconstriction and Shivering Thresholds

Background: Clonidine decreases the vasoconstriction and shivering thresholds. It thus seems likely that the alpha2 agonist dexmedetomidine will also impair control of body temperature. Accordingly, the authors evaluated the dose‐dependent effects of dexmedetomidine on the sweating, vasoconstriction, and shivering thresholds. They also measured the effects of dexmedetomidine on heart rate, blood pressures, and plasma catecholamine concentrations. Methods: Nine male volunteers participated in this randomized, double‐blind, cross‐over protocol. The study drug was administered by computer‐controlled infusion, targeting plasma dexmedetomidine concentrations of 0.0, 0.3, and 0.6 ng/ml. Each day, skin and core temperatures were increased to provoke sweating and then subsequently reduced to elicit vasoconstriction and shivering. Core‐temperature thresholds were computed using established linear cutaneous contributions to control of sweating, vasoconstriction, and shivering. The dose‐dependent effects of dexmedetomidine on thermoregulatory response thresholds were then determined using linear regression. Heart rate, arterial blood pressures, and plasma catecholamine concentrations were determined at baseline and at each threshold. Results: Neither dexmedetomidine concentration increased the sweating threshold from control values. In contrast, dexmedetomidine administration reduced the vasoconstriction threshold by 1.61 +/‐ 0.80 [degree sign] Celsius [center dot] ng sup ‐1 [center dot] ml (mean +/‐ SD) and the shivering threshold by 2.40 +/‐ 0.90 [degree sign] Celsius [center dot] ng sup ‐1 [center dot] ml. Hemodynamic responses and catecholamine concentrations were reduced from baseline values, but they did not differ at the two tested dexmedetomidine doses. Conclusions: Dexmedetomidine markedly increased the range of temperatures not triggering thermoregulatory defenses. The drug is thus likely to promote hypothermia in a typical hospital environment; it is also likely to prove an effective treatment for shivering.

Treatment of postoperative nausea and vomiting after outpatient surgery with the 5-HT3 antagonist ondansetron.

BackgroundPostoperative nausea and vomiting following outpatient surgery can significantly delay discharge. This study evaluates the safety and efficacy of ondansetron (a new 5-HT, antagonist) in the treatment of postoperative nausea and vomiting in patients following outpatient surgery. MethodsFive hundred outpatient surgical patients (53 male and 447 female), receiving general endotracheal anesthesia, were studied at ten centers. Patients were stratified by gender and received, in a randomized, double-blind manner, 1, 4, or 8 mg ondansetron or placebo in response to nausea and/or vomiting postoperatively. Episodes of vomiting, nausea scores, adverse events, vital signs, and laboratory values were evaluated before and during the 24 h after study drug administration. ResultsComplete response to study medication (no vomiting and/or retching, and no rescue antiemetic over the initial 0–2-h period) was more frequent in the ondansetron groups (1 mg 57%, 4 mg 61%, and 8 mg 57%) than in the placebo group (30%, P <.001). For the 0–24-h study a complete response occurred in only 15% of the placebo group compared to 41%, 47%, and 47% of the 1-, 4-, and 8-mg ondansetron groups, respectively (P <.001 for all comparisons with placebo). Median nausea scores (range 0–10) during the initial observation period (0–2 h) were significantly lower for all doses of ondansetron (1.3, 0.8, 1.8 for 1, 4, and 8 mg, respectively) as compared with placebo (2.3). No significant differences occurred in hemodynamic stability, incidence of adverse events, or changes in laboratory values in the ondansetron groups compared to the placebo group. ConclusionsOndansetron, in doses less than 8 mg, is a safe, effective antiemetic for treating postoperative nausea and vomiting.

Subthalamic nucleus deep brain stimulator placement using high-field interventional magnetic resonance imaging and a skull-mounted aiming device: technique and application accuracy.

OBJECTnThe authors discuss their method for placement of deep brain stimulation (DBS) electrodes using interventional MR (iMR) imaging and report on the accuracy of the technique, its initial clinical efficacy, and associated complications in a consecutive series of subthalamic nucleus (STN) DBS implants to treat Parkinson disease (PD).nnnMETHODSnA skull-mounted aiming device (Medtronic NexFrame) was used in conjunction with real-time MR imaging (Philips Intera 1.5T). Preoperative imaging, DBS implantation, and postimplantation MR imaging were integrated into a single procedure performed with the patient in a state of general anesthesia. Accuracy of implantation was assessed using 2 types of measurements: the radial error, defined as the scalar distance between the location of the intended target and the actual location of the guidance sheath in the axial plane 4 mm inferior to the commissures, and the tip error, defined as the vector distance between the expected anterior commissure-posterior commissure (AC-PC) coordinates of the permanent DBS lead tip and the actual AC-PC coordinates of the lead tip. Clinical outcome was assessed using the Unified Parkinsons Disease Rating Scale part III (UPDRS III), in the off-medication state.nnnRESULTSnTwenty-nine patients with PD underwent iMR imaging-guided placement of 53 DBS electrodes into the STN. The mean (+/- SD) radial error was 1.2 +/- 0.65 mm, and the mean absolute tip error was 2.2 +/- 0.92 mm. The tip error was significantly smaller than for STN DBS electrodes implanted using traditional frame-based stereotaxy (3.1 +/- 1.41 mm). Eighty-seven percent of leads were placed with a single brain penetration. No hematomas were visible on MR images. Two device infections occurred early in the series. In bilaterally implanted patients, the mean improvement on the UPDRS III at 9 months postimplantation was 60%.nnnCONCLUSIONSnThe authors technical approach to placement of DBS electrodes adapts the procedure to a standard configuration 1.5-T diagnostic MR imaging scanner in a radiology suite. This method simplifies DBS implantation by eliminating the use of the traditional stereotactic frame and the subsequent requirement for registration of the brain in stereotactic space and the need for physiological recording and patient cooperation. This method has improved accuracy compared with that of anatomical guidance using standard frame-based stereotaxy in conjunction with preoperative MR imaging.

Placement of deep brain stimulator electrodes using real-time high-field interventional magnetic resonance imaging

A methodology is presented for placing deep brain stimulator electrodes under direct MR image guidance. The technique utilized a small, skull‐mounted trajectory guide that is optimized for accurate alignment under MR fluoroscopy. Iterative confirmation scans are used to monitor device alignment and brain penetration. The methodology was initially tested in a human skull phantom and proved capable of achieving submillimeter accuracy over a set of 16 separate targets that were accessed. The maximum error that was obtained in this preliminary test was 2 mm, motivating use of the technique in a clinical study. Subsequently, a total of eight deep brain stimulation electrodes were placed in five patients. Satisfactory placement was achieved on the first pass in seven of eight electrodes, while two passes were required with one electrode. Mean error from the intended target on the first pass was 1.0 ± 0.8 mm (range = 0.1–1.9 mm). All procedures were considered technical successes and there were no intraoperative complications; however, one patient did develop a postoperative infection. Magn Reson Med, 2005.

Autonomic nervous system responses during sedative infusions of dexmedetomidine

BACKGROUNDnThe purpose of this study was to determine the effects of dexmedetomidine on systemic and cardiac autonomic reflex responses during rest and during thermal stress.nnnMETHODSnVolunteers received either placebo or low- or high-dose dexmedetomidine (target plasma concentrations 0.3 or 0.6 ng/ml, respectively) infusions in a prospectively randomized, double-blinded crossover study design. After 1 h, baroreflex sensitivity was assessed, and then core body temperature was raised to the sweating threshold and then lowered to the shivering threshold. Plasma catecholamines and blood pressure were measured, and cardiac autonomic responses were assessed by analysis of heart rate variability.nnnRESULTSnCompared with placebo, plasma norepinephrine concentrations, blood pressure, heart rate, and some heart rate variability measures were lower after 1-h infusion of dexmedetomidine, but baroreflex responses did not differ significantly. Dexmedetomidine blunted the systemic and cardiac sympathetic effects of sweating observed during placebo infusion but had no effect on parasympathetic measures. Increases in blood pressure, and systemic catecholamines due to shivering were observed during placebo and dexmedetomidine, but these responses were less with dexmedetomidine. During shivering, dexmedetomidine infusion was associated with higher low-frequency and high-frequency heart rate variability power but lower heart rate compared with the sweating threshold and with the control period, suggesting nonreciprocal cardiac autonomic responses.nnnCONCLUSIONSnInfusion of dexmedetomidine results in compensated reductions in systemic sympathetic tone without changes in baroreflex sensitivity. Dexmedetomidine blunts heart rate and the systemic sympathetic activation due to sweating, but it is less effective in blunting cardiac sympathetic responses to shivering. During dexmedetomidine infusion, cardiac sympathetic and parasympathetic tone may have nonreciprocal changes during shivering.

Society for Neuroscience in Anesthesiology and Critical Care Expert Consensus Statement: Anesthetic Management of Endovascular Treatment for Acute Ischemic Stroke* Endorsed by the Society of NeuroInterventional Surgery and the Neurocritical Care Society

Literature on the anesthetic management of endovascular treatment of acute ischemic stroke (AIS) is limited. Anesthetic management during these procedures is still mostly dependent on individual or institutional preferences. Thus, the Society of Neuroscience in Anesthesiology and Critical Care (SNACC) created a task force to provide expert consensus recommendations on anesthetic management of endovascular treatment of AIS. The task force conducted a systematic literature review (up to August 2012). Because of the limited number of research articles relating to this subject, the task force solicited opinions from experts in this area. The task force created a draft consensus statement based on the available data. Classes of recommendations and levels of evidence were assigned to articles specifically addressing anesthetic management during endovascular treatment of stroke using the standard American Heart Association evidence rating scheme. The draft consensus statement was reviewed by the Task Force, SNACC Executive Committee and representatives of Society of NeuroInterventional Surgery (SNIS) and Neurocritical Care Society (NCS) reaching consensus on the final document. For this consensus statement the anesthetic management of endovascular treatment of AIS was subdivided into 12 topics. Each topic includes a summary of available data followed by recommendations. This consensus statement is intended for use by individuals involved in the care of patients with acute ischemic stroke, such as anesthesiologists, interventional neuroradiologists, neurologists, neurointensivists, and neurosurgeons.

Measurement of the low-frequency component of blood pressure variability can assist the interpretation of heart rate variability data.

To the Editor:—Dowd et al. have provided important information about the pharmacokinetics of tranexamic acid (TA) in cardiac surgery with cardiopulmonary bypass. Particularly, they demonstrated the necessity of a continuous infusion of TA to obtain stable therapeutic concentrations. Then, they proposed two different dosage schemes in lowand high-risk patients for bleeding, to obtain TA plasma concentrations of 334 M and 800 M, respectively. Considering the patients with low-risk for bleeding, they recommended a loading dose of 12.5 mg/kg (or greater) over 30 min, a continuous infusion of 6.5 mg · kg 1 · hr , and 1 mg/kg (or greater) added to the priming, whereas in patients with high-risk for bleeding they proposed doses about 2.5 higher. My group published various studies proposing an original pharmacologic protocol for TA that seem very similar to that proposed by Down et al. For patients with low-risk for bleeding; that is, a loading dose of 1 g over 20 min before sternotomy (and not 1 g, 20 min before sternotomy, as erroneously reported in the work of my group cited by Dowd et al.), followed by a continuous infusion of 400 mg/h, and 500 mg added to pump priming. We also applied the same protocol in high-risk patients for bleeding, obtaining a significant reduction of blood loss and allogeneic transfusions. One criticism of the study of Dowd et al. is that the need to increase the doses of TA in this type of patient requires further clinical demonstrations, particularly considering (as the same authors report) that TA plasma concentrations of about 200 M completely inhibit fibrinolysis. Concerning the administration of TA after surgery, I agree with Dowd et al. regarding benefits in the postoperative period depending on intraoperative dosing techniques, but I do not understand why the authors claim that the efficacy of prolonged TA administration in the postoperative period is an open question. In reality, the authors, applying their pharmacokinetic model to our TA protocol, confirmed the conclusions of our study. Our intraoperative TA dosage scheme guarantees therapeutic concentrations for about 12 h, rendering unnecessary postoperative infusion of the drug. It also seems that the potential thrombotic risk intrinsic to antifibrinolytic drugs is underestimated by Down et al. I particularly disagree with their statement, “TA appears to be a very safe medication. . .. Thus our attempt to avoid excessive TA concentrations may not be necessary.” An extensive literature search showed cases of thrombosis following the use of hemostatic drugs such as -aminocaproic acid, aprotinin, and TA, but it would be sufficient to cite a recent case report describing two fatal cases of thrombosis after the use of -aminocaproic acid (very similar to TA with a potency 10 times lower) in cardiac surgical patients operated on with deep hypothermic circulatory arrest, wherein postmortem laboratory analysis revealed the presence of Factor V Leiden. Because it is impossible to identify patients with a preoperative prothrombotic state, it is appropriate to use the minimal effective doses of hemostatic drugs to avoid amplifying these thrombotic complications. Furthermore, the same authors’ group reported in a previous study three cases of stroke in cardiac surgical patients with known peripheral vascular disease, treated intraoperatively with high doses of TA. One would speculate that high concentrations of TA facilitated the formation of a thrombus in the presence of blood flow reductions in a diseased vessel. In conclusion, only large, prospective, blinded studies will establish the real safety and efficacy of the various doses of tranexamic acid in cardiac surgery. Currently, caution is required when using a hemostatic drug.

Amount of Air Infused to Patient Increases as Fluid Flow Rates Decrease When Using the Hotline® HL-90 Fluid Warmer

Objective. The intraoperative use of fluid warming devices has been recommended to avoid perioperative hypothermia and related adverse outcomes. To evaluate whether these devices might introduce risks of their own, we measured the volume of air escaping from a warmed intravenous solution that might be delivered to a patient. Methods. In an operating room maintained at 19–19.5 °C, we tested an HL-90 Hotline® fluid warmer with the L-70 fluid warming set. One liter of lactated Ringers solution was infused at flow rates of 150, 300, 500 and 3400 ml/h. The air that formed within the L-70 tubing during infusion was collected in a bubble trap placed at the end of the L-70 tubing. The volume of air in the bubble trap was measured. Twelve separate measurements were obtained at each flow rate. One additional study (n = 8) was performed using the L-10 Gas Vent to determine whether this equipment might reduce the volume of air infused when fluid flow rate was 300 mL/h. The volume of air collected at each flow rate was compared using ANOVA. Results. Volume of air increased significantly from 1.0 ± 0.2 mL to 2.9 ± 0.4 ml as flow rate decreased from 3400 ml/h to 150 ml/h (p < 0.0001). The L-10 gas eliminator was ineffective in reducing the amount of air infused. Conclusions. We conclude that the use of the Hotline® fluid warmer can result in infusion of air into the patient, introducing possible risk of air embolism.

Dose-response study of oral famotidine for reduction of gastric acidity and volume in outpatients and inpatients.

A relatively new H2-antagonist, famotidine, has become clinically available, but its effectiveness in decreasing gastric acidity and volume has not been compared in inpatients and outpatients. We reexamined the difference in gastric acidity and volume in inpatients and outpatients, and tested the effectiveness of different oral doses and dosage regimens of famotidine in reducing gastric acidity and volume in both groups of patients. Patients received either placebo or 20 mg or 40 mg of famotidine orally the night before surgery (HS) and on the morning of surgery (AM). One hundred forty-two inpatients and 180 outpatients were randomized to one of seven groups as follows: 1) placebo (HS)/placebo (AM); 2) 20 mg of famotidine (HS)/20 mg of famotidine (AM); 3) 20 mg of famotidine (HS)/placebo (AM); 4) placebo (HS)/20 mg of famotidine (AM); 5) 40 mg of famotidine (HS)/40 mg of famotidine (AM); 6) 40 mg of famotidine (HS)/placebo (AM); and 7) placebo (HS)/40 mg of famotidine (AM). We measured the gastric acidity and volume after induction of anesthesia and found no difference between the inpatients and outpatients, with or without famotidine. We found that famotidine given HS and AM or AM only was effective in reducing gastric acidity in both groups of patients, and that there was no difference between the 20-mg and 40-mg doses of famotidine. Gastric volume was not affected by any famotidine dose.