Peter H. Tonner

Dexmedetomidine in anaesthesia.

Purpose of review The development of dexmedetomidine, a potent and highly selective α2-adrenoceptor agonist, has created new interest in the use of α2-adrenoceptor agonists, and has led to its evaluation in various yet non-approved perioperative settings. The current review focuses on the usefulness of dexmedetomidine in anaesthesia practice. Recent findings Recently acquired knowledge and experience with dexmedetomidine in perioperative use will be presented and discussed in the context of known pharmacological properties. Summary Dexmedetomidine offers beneficial pharmacological properties, providing dose-dependent sedation, analgesia, sympatholysis and anxiolysis without relevant respiratory depression. The side-effects are predictable from the pharmacological profile of (2-adrenoceptor agonists. In particular, the unique sedative properties of dexmedetomidine resulted in several interesting applications in anaesthesia practice, promising benefits in the perioperative use of this compound. However, dexmedetomidine was approved for sedation in the intensive care unit in the USA in 1999, and administration in anaesthesia practice remains an ‘off-label’ use. Further studies are needed to establish the role of dexmedetomidine in the perioperative period.

Overlapping induction of anesthesia: an analysis of benefits and costs.

Background:Overlapping induction (OI), i.e., induction of anesthesia with an additional team while the previous patient is still in the operating room (OR), was investigated. Methods:The study period was 60 days in two followed by three ORs during surgical Block Time (7:30 am until 3:00 pm). Patients were admitted the day before surgery and were thus available and did not have surgery that day unless there was a time reduction. Facilities were already constructed. Number of cases, Nonsurgical Time (Skin Suture Finish until next Procedure Start Time), Turnover Time, and Anesthesia Control Time plus Turnover Time were studied. In addition, economic benefit was calculated. Results:Three hundred thirty-five cases were studied. Using OI, the time of care of regularly scheduled cases was shortened, and the number of cases performed within OR Block Time increased (151 to 184 cases; P < 0.05). Nonsurgical Time (in h:min) decreased (1:08 ± 0:26 to 0:57 ± 0:18; P < 0.001), Turnover Time decreased (0:38 ± 0:24 to 0:25 ± 0:15; P < 0.05), and Anesthesia Control Time plus Turnover Time decreased (0:43 ± 0:23 to 0:28 ± 0:18; P < 0.001). Subgroup analysis showed a significant benefit of OI only in three ORs. In three ORs, economic benefit can be gained at a case mix index greater than 0.3 besides additional costs. Conclusions:Overlapping induction increased productivity and profit despite the expense of additional staff. Subgroup analysis emphasizes the importance of the number of ORs involved in OI.

Evidence and consensus-based German guidelines for the management of analgesia, sedation and delirium in intensive care--short version.

Targeted monitoring of analgesia, sedation and delirium, as well as their appropriate management in critically ill patients is a standard of care in intensive care medicine. With the undisputed advantages of goal-oriented therapy established, there was a need to develop our own guidelines on analgesia and sedation in intensive care in Germany and these were published as 2nd Generation Guidelines in 2005. Through the dissemination of these guidelines in 2006, use of monitoring was shown to have improved from 8 to 51% and the use of protocol-based approaches increased to 46% (from 21%). Between 2006–2009, the existing guidelines from the DGAI (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin) and DIVI (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin) were developed into 3rd Generation Guidelines for the securing and optimization of quality of analgesia, sedation and delirium management in the intensive care unit (ICU). In collaboration with another 10 professional societies, the literature has been reviewed using the criteria of the Oxford Center of Evidence Based Medicine. Using data from 671 reference works, text, diagrams and recommendations were drawn up. In the recommendations, Grade “A” (very strong recommendation), Grade “B” (strong recommendation) and Grade “0” (open recommendation) were agreed. As a result of this process we now have an interdisciplinary and consensus-based set of 3rd Generation Guidelines that take into account all critically illness patient populations. The use of protocols for analgesia, sedation and treatment of delirium are repeatedly demonstrated. These guidelines offer treatment recommendations for the ICU team. The implementation of scores and protocols into routine ICU practice is necessary for their success.

Neuroendocrine stress response and heart rate variability: a comparison of total intravenous versus balanced anesthesia.

Attenuating intraoperative stress is a key factor in improving outcome. We compared neuroendocrine changes and heart rate variability (HRV) during balanced anesthesia (BAL) versus total IV anesthesia (TIVA). Forty-three patients randomly received either BAL (sevoflurane/remifentanil) or TIVA (propofol/remifentanil). Depth of anesthesia was monitored by bispectral index. Stress hormones were measured at 7 time points (P1 = baseline; P2 = tracheal intubation; P3 = skin incision; P4 = maximum operative trauma; P5 = end of surgery; P6 = tracheal extubation; P7 = 15 min after tracheal extubation). HRV was analyzed by power spectrum analysis: very low frequency (VLF), low frequency (LF), high frequency (HF), LF/HF ratio, and total power (TP). LF/HF was higher in TIVA at P6 and TP was higher in TIVA at P3–7 (P3: 412.6 versus 94.2; P4: 266.7 versus 114.6; P5: 290.3 versus 111.9; P6: 1523.7 versus 658.1; P7: 1225.6 versus 342.6 ms2). BAL showed higher levels of epinephrine (P7: 100.5 versus 54 pg/mL), norepinephrine (P3: 221 versus 119.5; P4: 194 versus 130.5 pg/mL), adrenocorticotropic hormone (P2 10.5 versus 7.7; P5: 5.3 versus 3.6; P6: 10.9 versus 5.3; P7: 20.5 versus 7.1 pg/mL) and cortisol (P7: 6.9 versus 3.9 &mgr;g/dL). This indicates a higher sympathetic outflow using BAL versus TIVA during ear-nose-throat surgery.

Sevoflurane but not propofol preserves myocardial function during minimally invasive direct coronary artery bypass surgery.

Volatile anesthetics exert cardioprotective properties in experimental and clinical studies. We designed this study to investigate the effects of sevoflurane on left ventricular (LV) performance during minimally invasive direct coronary artery bypass grafting (MIDCAB) without cardiopulmonary bypass. Fifty-two patients scheduled for MIDCAB surgery were randomly assigned to a propofol or a sevoflurane group. Apart from the anesthetics used, there was no difference in surgical and anesthetic management. After determination of cardiac troponin T, creatine kinase, and creatine kinase MB, electrocardiographic (ECG) data and echocardiography variables (myocardial performance index and early to atrial filling velocity ratio) the left anterior descending coronary artery (LAD) was clamped until anastomosis with the left internal mammary artery was completed. During LAD occlusion and during reperfusion, echocardiography measurements were repeated. Blood samples were obtained repeatedly for up to 72 h. After LAD occlusion, myocardial performance index and early to atrial filling velocity ratio in the propofol group deteriorated significantly from 0.40 ± 0.12 and 1.29 ± 0.35 to 0.49 ± 0.10 and 1.13 ± 0.22, respectively, whereas there was no change in the sevoflurane group. In the propofol group myocardial performance index remained increased (0.47 ± 0.11) compared with baseline during reperfusion. There were no significant differences in ECG and laboratory values between groups. In conclusion, during a brief period of ischemia in patients undergoing MIDCAB surgery, sevoflurane preserved myocardial function better than propofol.

Heart Rate Variability Predicts Severe Hypotension after Spinal Anesthesia for Elective Cesarean Delivery

Background:Hypotension due to vasodilation during subarachnoid block (SAB) for elective cesarean delivery may be harmful. Heart rate variability (HRV), reflecting autonomic control, may identify patients at risk of hypotension. Methods:Retrospectively, HRV was analyzed in 41 patients who were classified into one of three groups depending on the decrease in systolic blood pressure (SBP): mild (SBP > 100 mmHg), moderate (100 > SBP > 80 mmHg), or severe (SBP < 80 mmHg). Prospectively, HRV and hemodynamic data of 19 patients were studied. Relative low frequency (LF), relative high frequency (HF), and LF/HF ratio were analyzed. Results:Retrospective analysis of HRV showed a significantly higher sympathetic and lower parasympathetic drive in the groups with moderate and severe compared with mild hypotension before SAB (median, 25th/75th percentiles): LF/HF: mild: 1.2 (0.9/1.8), moderate: 2.8 (1.8/4.6), P < 0.05 versus mild; severe: 2.7 (2.0/3.5), P < 0.05 versus mild. Results were confirmed by findings of LF and HF. Prospectively, patients were grouped according to LF/HF before SAB: low-LF/HF: 1.5 (1.1/2.0) versus high-LF/HF: 4.0 (2.8/4.7), P < 0.05; low-LF: 58 ± 9% versus high-LF: 75 ± 10%, P < 0.05; low-HF: 41 ± 10% versus high-HF: 25 ± 10%, P < 0.05. High-risk patients had a significantly lower SBP after SAB (76 ± 21 vs. 111 ± 12 mmHg; P < 0.05). Conclusions:Retrospectively analyzed HRV of patients scheduled to undergo elective cesarean delivery during SAB showed significant differences depending on the severity of hypotension after SAB. Preliminary findings were prospectively confirmed. High LF/HF before SAB predicted severe hypotension. Preoperative HRV analysis may detect patients at risk of hypotension after SAB.

Propofol infusion syndrome in anaesthesia and intensive care medicine.

Purpose of review Propofol infusion syndrome is a rare but often fatal syndrome, characterized by lactacidosis, lipaemic plasma and cardiac failure, associated with propofol infusion over prolonged periods of time. As propofol is used worldwide, knowledge of propofol infusion syndrome is essential for all anaesthesiologists and intensive care physicians. This review will provide an update on reported cases, and describe recent findings relevant to the pathophysiology and clinical presentation of propofol infusion syndrome. Recent findings Case reports of propofol infusion syndrome have contributed new pathophysiological evidence. Reported cases of similar syndromes may represent initial propofol infusion syndrome, and may help to identify further risk factors such as low carbohydrate supply and early warning signs such as lactacidosis. Newly identified gene defects mimicking propofol infusion syndrome may elicit the underlying genetic susceptibility. Recommendations for the limitation of propofol use have been devised by various institutions. Summary Propofol infusion syndrome must be kept in mind as a rare but highly lethal complication of propofol use, not necessarily confined to the prolonged use of propofol. Dose limitations must be adhered to, and early warning signs such as lactacidosis should lead to the immediate cessation of propofol infusion.

Multicenter randomized comparison of xenon and isoflurane on left ventricular function in patients undergoing elective surgery

Background: Volatile anesthetics are commonly used for general anesthesia. However, these can induce profound cardiovascular alterations. Xenon is a noble gas with potent anesthetic and analgesic properties. However, it is uncertain whether xenon alters myocardial function. The aim of this study was therefore to investigate left ventricular function during anesthesia with xenon compared with isoflurane. Methods: The authors performed a randomized multicenter trial to compare xenon with isoflurane with respect to cardiovascular stability and adverse effects in patients without cardiac diseases scheduled for elective surgery. Two hundred fifty-nine patients were enrolled in this trial, of which 252 completed the study according to the protocol. Patients were anesthetized with xenon or isoflurane, respectively. Before administration of the study drugs and at four time points, the effects of both anesthetics on left ventricular function were investigated using transesophageal echocardiography. Results: Global hemodynamic parameters were significantly altered using isoflurane (P < 0.05 vs. baseline), whereas xenon only decreased heart rate (P < 0.05 vs. baseline). In contrast to xenon, left ventricular end-systolic wall stress decreased significantly in the isoflurane group (P < 0.05 vs. baseline). Velocity of circumferential fiber shortening was decreased significantly in the xenon group but showed a more pronounced reduction during isoflurane administration (P < 0.05 vs. baseline). The contractile index (difference between expected and actually measured velocity of circumferential fiber shortening) as an independent parameter for left ventricular function was significantly decreased after isoflurane (P < 0.0001) but unchanged using xenon. Conclusions: Xenon did not reduce contractility, whereas isoflurane decreased the contractile index, indicating that xenon enables favorable cardiovascular stability in patients without cardiac diseases.

The effects of dexmedetomidine on perinatal excitotoxic brain injury are mediated by the alpha2A-adrenoceptor subtype.

We performed the current study in mice lacking individual α2-adrenoceptor subtypes to elucidate the contribution of α2-adrenoceptor subtypes to the neuroprotective properties of dexmedetomidine in a model of perinatal excitotoxic brain injury. On postnatal Day 5, wild-type mice and mice lacking α2A-adrenoceptor (α2A-KO) or α2C-adrenoceptor subtypes (α2C-KO) were randomly assigned to receive dexmedetomidine (3 &mgr;g/kg) or phosphate-buffered saline intraperitoneally. Thirty minutes after the intraperitoneal injection, the glutamatergic agonist ibotenate (10 &mgr;g) was intracerebrally injected, producing transcortical necrosis and white matter lesions that mimic perinatal human hypoxic-like lesions. Quantification of the lesions was performed on postnatal Day 10 by histopathologic examination. Dexmedetomidine reduced mean lesion size in the cortex of wild-type mice and α2C-KO mice by 44% and 49%, respectively. Ibotenate-induced white matter lesions were reduced by 71% (wild-type mice) and 75% (α2C-KO mice) after pretreatment with dexmedetomidine. In contrast, in α2A-KO mice, dexmedetomidine did not protect against the cortical excitotoxic insult, and white matter lesions were even more pronounced (82% increase of mean lesion size). Dexmedetomidine provides potent neuroprotection in a model of perinatal excitotoxic brain damage. This effect was completely abolished in α2A-KO mice, suggesting that the neuroprotective effect is mediated via the α2A-adrenoceptor subtype.

A comparison of the intubating laryngeal mask airway and the Bonfils intubation fibrescope in patients with predicted difficult airways

Tracheal intubation with the intubating laryngeal mask airway or the Bonfils intubation fibrescope was performed in 80 patients with predicted difficult airways. Mallampati score, thyromental distance, mouth opening and mobility of the atlanto‐occipital joint were used to predict difficult airways. The overall success rate, time to the first adequate lung ventilation and time taken for the successful placement of the tracheal tube were recorded, as well as a subjective assessment of the handling of the device and the incidence of postoperative sore throat and hoarseness. The median [range] time to the first adequate ventilation was significantly shorter with the intubating laryngeal mask airway than with the Bonfils intubation fibrescope (28 [6–85] s vs. 40 [23–77] s, p < 0.005). Tracheal intubation was significantly slower with the intubating laryngeal mask airway than with the Bonfils intubation fibrescope (76 [45–155] s vs. 40 [23–77] s, p < 0.0001. Patients in the Bonfils group suffered less sore throat and hoarseness than those in the other group.