International multicentre review of perioperative management and outcome for catecholamine-producing tumours.

BACKGROUND: Surgery for catecholamine-producing tumours can be complicated by intraoperative and postoperative haemodynamic instability. Several perioperative management strategies have emerged but none has been evaluated in randomized trials. To assess this issue, contemporary perioperative management and outcome data from 21 centres were collected. METHODS: Twenty-one centres contributed outcome data from patients who had surgery for phaeochromocytoma and paraganglioma between 2000 and 2017. The data included the number of patients with and without α-receptor blockade, surgical and anaesthetic techniques, complications and perioperative mortality. RESULTS: Across all centres, data were reported on 1860 patients with phaeochromocytoma or paraganglioma, of whom 343 underwent surgery without α-receptor blockade. The majority of operations (78·9 per cent) were performed using minimally invasive techniques, including 16·1 per cent adrenal cortex-sparing procedures. The cardiovascular complication rate was 5·0 per cent overall: 5·9 per cent (90 of 1517) in patients with preoperative α-receptor blockade and 0·9 per cent (3 of 343) among patients without α-receptor blockade. The mortality rate was 0·5 per cent overall (9 of 1860): 0·5 per cent (8 of 517) in pretreated and 0·3 per cent (1 of 343) in non-pretreated patients. CONCLUSION: There is substantial variability in the perioperative management of catecholamine-producing tumours, yet the overall complication rate is low. Further studies are needed to better define the optimal management approach, and reappraisal of international perioperative guidelines appears desirable.

ANTECEDENTES: La cirugía de los tumores productores de catecolaminas puede complicarse por la inestabilidad hemodinámica intraoperatoria y postoperatoria. Se han propuesto distintas estrategias de manejo perioperatorio, pero ninguna ha sido evaluada en ensayos aleatorizados. Para evaluar este tema, se han recogido los datos de los resultados y del manejo perioperatorio contemporáneo de 21 centros. MÉTODOS: Veintiún centros aportaron datos de los resultados de los pacientes operados por feocromocitoma y paraganglioma entre 2000-2017. Los datos incluyeron el número de pacientes con y sin bloqueo del receptor α, las técnicas quirúrgicas y anestésicas, las complicaciones y la mortalidad perioperatoria. RESULTADOS: Los centros en su conjunto aportaron datos de 1.860 pacientes con feocromocitoma y paraganglioma, de los cuales 343 pacientes fueron intervenidos sin bloqueo del receptor α. La gran mayoría (79%) de las cirugías se realizaron utilizando técnicas mínimamente invasivas, incluido un 17% de procedimientos con preservación de la corteza suprarrenal. La tasa de complicaciones cardiovasculares fue de 5,0% en total; 5,9% (90/1517) en pacientes con bloqueo preoperatorio de los receptores α y 0,9% (3/343) en pacientes no pretratados. La mortalidad global fue del 0,5% (9/1860); 0,5% (8/1517) en pacientes pretratados y 0,3% (1/343) en pacientes no tratados previamente. CONCLUSIÓN: Existe una variabilidad sustancial en el manejo perioperatorio de los tumores productores de catecolaminas, aunque la tasa global de complicaciones es baja. Este estudio brinda la oportunidad para efectuar comparaciones sistemáticas entre estrategias de prácticas terapéuticas variables. Se necesitan más estudios para definir mejor el enfoque de manejo óptimo y parece conveniente volver a evaluar las guías internacionales perioperatorias.

Perioperative α-receptor blockade in phaeochromocytoma surgery: an observational case series.

BACKGROUND: Mortality associated with surgery for phaeochromocytoma has dramatically decreased over the last decades. Many factors contributed to the dramatic decline of the mortality rate, and the influence of an α-receptor blockade is unclear and has never been tested in a randomized trial. We evaluated intraoperative haemodynamic conditions and the incidence of complications in patients with and without α-receptor blockade undergoing surgery for catecholamine producing tumours. METHODS: Haemodynamic conditions and perioperative complications were assessed in 110 patients with (B) and 166 without (N) α-receptor blockade. Data were analysed as a consecutive case series of 303 cases and subsequently via propensity score matching, and presented as mean and confidence interval (CI). RESULTS: No difference in maximal intraoperative systolic arterial pressures (B = 178 mm Hg (CI 169-187) vs N = 185 mm Hg (CI 177-193; P = 0.2542) and hypertensive episodes above 250 mm Hg were found (P = 0.7474) for the closed case series. No major complications occurred. Propensity score matching (75 pairs) revealed a significant difference of 17 mm Hg in maximal intraoperative systolic bp for these selected pairs (P = 0.024). CONCLUSIONS: Only a slight difference in mean maximal systolic arterial pressure was detected between patients with or without an α-receptor blockade. There was no difference in the incidence of excessive hypertensive episodes between groups and no major complications occurred. The basis for the general recommendation of perioperative α- receptor blockade for phaeochromocytoma surgery demands further study.

[Anesthetic management during pheochromocytoma surgery : Current strategies]. / Anästhesiologisches Management bei Phäochromozytomoperationen : Aktuelle Strategien.

BACKGROUND: Surgery-related mortality in patients with pheochromocytoma or paraganglioma has dramatically decreased over the last few decades. This effect has often been attributed to perioperative α­receptor blockade. However, this has never been tested in a randomized trial and many other changes have contributed to this improvement. At the same time α­receptor blockade was introduced, short-acting and well controllable agents became available for intraoperative arterial blood pressure management. Subsequently, surgical techniques improved and led almost exclusively to minimally invasive techniques, while improvements in the diagnostic techniques allow earlier and more precise detection of catecholamine-producing tumors. METHODS: Conduction of a randomized, controlled study to investigate the effect of α­receptor blockade on mortality is hampered by the rarity of the disease. With the currently low mortality rate, several thousands of patients would be needed to test such a hypothesis. Accordingly, intraoperative management is generally based on expert opinion. Hypertensive episodes are treated by intravenous administration of sodium nitroprusside, urapidil or nitroglycerine. Depending on the individual case a short-acting ß­blocker and magnesium might be added. Hypotension following tumor removal is treated with intravenous fluid infusion and continuous norepinephrine administration. Adrenal gland-sparing resection of pheochromocytoma does not seem to increase the risk of arterial hypertension. CONCLUSION: Future research should focus on identification of risk factors for intraoperative hypertensive episodes and the question whether a time-consuming, unreliable α­receptor blockade, burdened with significant side effects, is still needed.

Fibreoptic vs videolaryngoscopic (C-MAC(®) D-BLADE) nasal awake intubation under local anaesthesia.

Numerous indirect laryngoscopes have been introduced into clinical practice and their use for tracheal intubation under local anaesthesia has been described. However, a study comparing indirect laryngoscopic vs fibreoptic intubation under local anaesthesia and sedation appears lacking. Therefore, we evaluated both techniques in 100 patients with an anticipated difficult nasal intubation time for intubation the primary outcome. We also assessed success rate, glottic view, Ramsey score, and patients' and anaesthetists' satisfaction. The median (IQR [range]) time for intubation was significantly shorter with the videolaryngoscope with 38 (24-65 [11-420]) s vs 94 (48-323 [19-1020]) s (p < 0.0001). There was no difference in the success rate of intubation (96% for both techniques; p > 0.9999) and satisfaction of the anaesthetists and patients. We conclude that in anticipated difficult nasal intubation a videolaryngoscope represents an acceptable alternative to fibreoptic intubation.

Effects of steep Trendelenburg position for robotic-assisted prostatectomies on intra- and extrathoracic airways in patients with or without chronic obstructive pulmonary disease.

BACKGROUND: The use of the steep Trendelenburg position and abdominal CO2-insufflation during surgery can lead to significant reduction in pulmonary compliance and upper airway oedema. The postoperative time course of these effects and their influence on postoperative lung function is unknown. Therefore, we assessed intra- and extrathoracic airway resistance and nasal air flow in patients with or without chronic obstructive pulmonary disease (COPD) during robotic-assisted prostatectomy. METHODS: In 55 patients without and 20 patients with COPD spirometric measurements and nasal resistance were obtained before operation, 40 and 120 min, and 1 and 5 days after operation. We measured vital capacity (VC), forced expiratory volume in 1 s (FEV1), maximal mid-expiratory and inspiratory flow (MEF50, MIF50), arterial oxygen saturation, and nasal flow. The occurrence of postoperative conjunctival oedema (chemosis) was also assessed. RESULTS: In patients without COPD, MEF50/MIF50 increased and nasal flow decreased significantly after surgery (P<0.0001) and normalized within 24 h. VC and FEV1 decreased after operation with a nadir at 24 h and recovered to normal until the fifth day (P<0.0001). In patients with COPD, changes in MEF50/MIF50 and nasal flow were similar, while changes in VC and FEV1 lasted beyond the fifth day (P<0.0001). CONCLUSIONS: Robotic-assisted prostatectomy in the steep Trendelenburg position led to an increase in upper airway resistance directly after surgery that normalized within 24 h. The development of chemosis can be indicative of increased upper airway resistance. In patients without COPD, VC and FEV1 were reduced after surgery and recovered within 5 days, while in patients with COPD, the alteration lasted beyond 5 days.

[Anaesthesia for patients with obstructive airway diseases].

Obstructive lung diseases like asthma or chronic obstructive lung diseases have a high prevalence and are one of the four most frequent causes of death. Obstructive lung diseases can be significantly influenced by the choice of anesthetic techniques and anesthetic agents. Basically, the severity of the COPD and the degree of bronchial hyperreactivity will determine the perioperative anesthetic risk. This risk has to be assessed by a thorough preoperative evaluation and will give the rationale on which to decide for the adequate anaesthetic technique. In particular, airway instrumentation can cause severe reflex bronchoconstriction. The use of regional anaesthesia alone or in combination with general anaesthesia can help to avoid airway irritation and leads to reduced postoperative complications. Prophylactic antiobstructive treatment, volatile anesthetics, propofol, opioids, and an adequate choice of muscle relaxants minimize the anesthetic risk, when general anesthesia is required In case, despite all precautions intra-operative bronchospasm occurs, deepening of anaesthesia, repeated administration of beta2-adrenergic agents and parasympatholytics, and a single systemic dose of corticosteroids represent the main treatment options.

Tracheal intubation in patients with odentogenous abscesses and reduced mouth opening.

BACKGROUND: Odentogenous abscesses with involvement of the facial or cervical spaces can be life-threatening and often have to be drained under general anaesthesia. Trismus and swelling can make intubation with a Macintosh laryngoscope difficult or even impossible. However, indirect laryngoscopy has been successful when conventional direct laryngoscopy has failed. Therefore, we evaluated the efficacy of the Glidescope laryngoscope in patients with odentogenous abscesses and the improvement in mouth opening after neuromuscular block. METHODS: After approval of the ethics committee, 100 patients with odentogenous abscesses were randomized to undergo tracheal intubation with the Glidescope or Macintosh laryngoscope. Success rate, visualization of the glottis, intubation duration, and need for supporting manoeuvres were evaluated. RESULTS: Intubation with the Glidescope was always successful, while conventional intubation failed in 17 out of 50 patients (P<0.0001). In all patients in whom conventional tracheal intubation failed, a subsequent attempt with the Glidescope was successful. The view at the glottis (according to Cormack and Lehane; P<0.0001), intubation duration [34 s (CI 27-41) vs 67 s (CI 52-82), mean (95% confidence interval); P=0.0001], and need for supporting manoeuvres (P<0.0001) were significantly different. The inter-incisor distance improved overall with induction of anaesthesia from 2.0 cm (CI 1.8-2.2) to 2.6 cm (CI 2.3-2.9; P<0.0001) and was correlated with the duration of symptoms. CONCLUSIONS: In patients with odentogenous abscesses, the use of a Glidescope laryngoscope was associated with significantly faster tracheal intubation, with a better view, fewer supporting manoeuvres, and a higher success rate than with a conventional laryngoscope. Improvement of the inter-incisor distance after induction of anaesthesia correlated with the duration of symptoms.

Nasotracheal intubation with three indirect laryngoscopes assisted by standard or modified Magill forceps.

We assessed the effect of modifying standard Magill forceps on the laryngeal introduction of an Eschmann stylet during nasotracheal intubations with three indirect laryngoscopes (Airtraq™, C-MAC(®) or GlideScope(®)) in patients with predicted difficult intubation. We allocated 50 participants to each laryngoscope. The stylet was advanced by one forceps followed by the other (standard or modified), with each sequence allocated to 25/50 for each laryngoscope. There were no differences in rates of failed tracheal intubation with the allocated laryngoscopes: 6/50, 5/50 and 5/50, respectively. An Eschmann stylet was advanced into the trachea less often with the standard forceps (65% vs 93%, p < 0.0001). Mean (SD) time for stylet advancement was longer with the standard forceps, 38 (30) vs 19 (19) s, p < 0.0001. In conclusion, the modified Magill forceps facilitated nasotracheal intubation, independent of the type of indirect laryngoscope.

[Preoperative α-receptor block in patients with pheochromocytoma? Against]. / Präoperative α-Rezeptoren-Blockade beim Phäochromozytom? - Kontra.

Perioperative mortality regarding the resection of catecholamine-producing tumors has been markedly improved. This improvement has been attributed to the preoperative treatment with α-receptor blocking agents. An α-receptor block is still recommended prior to the resection of pheochromocytoma or paraganglioma. However, the effect has never been tested in a randomized clinical trial. Despite an assumed effective α-receptor block, many centers report systolic blood pressure increases beyond 200 mmHg. Out of 200 consecutive resections of catecholamine-producing tumors, 73 patients without an α-receptor blockade were treated. There was no significant difference in the maximum systolic blood pressure or in the incidence of hypertensive episodes. There was no correlation between the individual dose of phenoxybenzamine and the maximum blood pressure. Overall it can be concluded that with the improvement of surgical techniques, diagnostic tools and highly effective short acting substances to control hemodynamics intraoperatively, the question must be raised whether a time-consuming, unreliable pretreatment burdened with significant side effects is still required.

Development and validation of a novel tool to estimate peri-operative blood loss.

Surgical blood loss predicts peri-operative outcomes. We have developed and validated Blood Loss Scores to estimate peri-operative blood loss during major abdominal surgery. Surgical blood loss and changes in haemoglobin concentration were recorded intra- and postoperatively for 48 h in 100 patients undergoing radical prostatectomy. Data from the first group (n = 50) were used to derive the Blood Loss Scores which were validated against the data from a second group (n = 50) at three time points (immediately postoperative and 24- and 48-h later). The score, taking into account suction fluid volume and haemoglobin concentration, explained more of the variance in the measured blood loss than the experts' assessment (77% vs 54%, p = 0.05) or the change in haemoglobin concentration (77% vs 11%, p < 0.0001). Addition of the change in haemoglobin concentration improved the estimate for the 24- and 48-h postoperative Blood Loss Scores to explain 78% and 80% of the variance of measured blood loss.

Easy and difficult nasal intubation--a randomised comparison of Macintosh vs Airtraq® laryngoscopes.

A new Airtraq(®) laryngoscope has been developed for nasal intubation. We prospectively compared tracheal intubation efficiency of the Airtraq for nasotracheal intubation vs that of the Macintosh laryngoscope in 200 patients. Depending on pre-operative airway evaluation, the patients were allocated to expected easy (n = 100) or difficult (n = 100) intubation groups, on the basis of mouth opening ≤ 2.5 cm, modified Mallampati score of 4, history of difficult intubation, obvious tumour or swelling. Patients were randomly allocated to the Macintosh or nasotracheal Airtraq technique. All easy intubations were successfully performed with the respective technique. In the expected difficult intubation group, the success rate was higher (47/50 vs 33/50; p < 0.01), the glottis view was better (Cormack and Lehane 1/2/3/4 grades: 29/17/1/3 vs 5/11/18/16, p < 0.01), mean (SD) intubation time was shorter (45(46) s vs 77(47)s, p < 0.01) and the number of optimising manoeuvres was reduced with the nasotracheal Airtraq compared with the Macintosh, respectively. For difficult nasal intubations, the nasotracheal Airtraq is more effective than the Macintosh laryngoscope.

Expected difficult tracheal intubation: a prospective comparison of direct laryngoscopy and video laryngoscopy in 200 patients.

BACKGROUND: The Berci-Kaplan video laryngoscope was developed to improve the visualization of the glottis and ease tracheal intubation. Whether this technique is also effective in patients with an expected difficult intubation is unclear. We have prospectively evaluated the conditions and success rate of tracheal intubation in patients with a Mallampati score of III or IV. METHODS: Two hundred patients, undergoing general anaesthesia, were randomized to be intubated using direct laryngoscopy (n=100) or video laryngoscopy (n=100). Visualization of the vocal cords, success rate, time for intubation, and the need for additional manoeuvres (laryngeal manipulations, head positioning, and Eschmann stylet) were evaluated. RESULTS: Video laryngoscopy produced better results for the visualization of the glottis using Cormack and Lehane criteria (P<0.001), success rate (n=92 vs 99, P=0.017), and the time for intubation [60 (77) vs 40 (31) s, P=0.0173]. In addition, the number of optimizing manoeuvres was also significantly decreased [1.2 (1.3) vs 0.5 (0.7), P<0.001]. CONCLUSIONS: Video laryngoscopy, when compared with direct laryngoscopy for difficult intubations, provides a significantly better view of the cords, a higher success rate, faster intubations, and less need for optimizing manoeuvres. Therefore, we feel that the video laryngoscopy leads to a clinically relevant improvement of intubation conditions and can be recommended for difficult airway management.

Genetic variability of induction and emergence times for inhalational anaesthetics.

BACKGROUND AND OBJECTIVES: Anaesthetic requirements differ among inbred mouse strains. We tested the genetic influence on induction and arousal times to inhalational anaesthetics in two of these strains. METHODS: Five male C57BL/6J (B6) and five male C3H/HeJ (C3) mice were each exposed to five different concentrations of nitrous oxide (N2O) at five different levels of halothane. Time to sleep and arousal were assessed. Data were analysed by repeated measures of analysis of variance. RESULTS: Halothane, N2O and genetic strain, all were significant independent factors on the time to sleep, while only N2O was a significant independent factor on the time to arousal (P = 0.004). B6 mice took significantly longer to fall asleep compared to the C3 mice controlling for halothane and N2O concentrations (F-ratio = 36, P < 0.0001). The effect of N2O on time to arousal was only significant for the B6 strain (F-ratio = 10, P = 0.005), and not for the C3 strain (F-ratio = 0.8, P = 0.38). CONCLUSIONS: Genetics influences the time to sleep for anaesthetic agents in mice.

Lidocaine exerts its effect on induced bronchospasm by mitigating reflexes, rather than by attenuation of smooth muscle contraction.

BACKGROUND: Lidocaine inhalation attenuates histamine-induced bronchoconstriction, as well as bronchoconstriction elicited by mechanical irritation. This effect could be mediated by direct effects on smooth muscle or by reflex attenuation. Therefore, we evaluated whether lidocaine attenuated the bronchial response of direct smooth muscle stimulation with methacholine. METHODS: In 15 volunteers with bronchial hyperreactivity, a methacholine challenge was performed following the inhalation of lidocaine, dyclonine (which does not attenuate bronchial reactivity) or saline on three different days in a randomized, double-blind fashion. Lung function, response to methacholine, and lidocaine and dyclonine plasma concentrations were measured. RESULTS: The inhaled methacholine concentration (PC20) necessary for a 20% decrease in the forced expiratory volume in 1 s (FEV1) was 8.8 +/- 6.1 mg/ml at the screening evaluation. The sensitivity to methacholine challenge (PC20) remained unchanged regardless of which solution was inhaled (9.1 +/- 7.5 mg/ml for lidocaine, 10.2 +/- 9.0 mg/ml for dyclonine and 9.8 +/- 8.3 mg/ml for saline; P = 0.58, means +/- standard deviation). Furthermore, the inhalation of all three solutions caused a significant decrease in FEV1 from baseline (P = 0.0007), with a significantly larger effect for dyclonine than lidocaine (P = 0.0153). CONCLUSIONS: Although both inhaled and intravenous lidocaine attenuates histamine-evoked bronchoconstriction, it does not alter the response to methacholine. Therefore, the attenuation of bronchial reactivity by lidocaine appears to be related solely to neurally mediated reflex attenuation, rather than to the attenuation of direct constriction of airway smooth muscle.

Expression of anion exchanger 3 influences respiratory rate in awake and isoflurane anesthetized mice.

The anion exchanger 3 (AE3) is involved in neuronal pH regulation of which may include chemosensitive neurons. Here we examined the effect of AE3 expression on respiratory rate (RR) in vivo. AE3 knockout (KO, n=5) and wild type (WT, n=6) mice were subjected to body plethysmography, both while awake and during isoflurane anesthesia. RR was significantly lower in awake AE3 KO (162+/-7SE min(-1)) than in WT mice (212+/-20 min(-1), P=0.036). The same was found during isoflurane anesthesia at 0.5 MAC (KO: 123+/-9 min(-1), WT: 168+/-15 min(-1), P=0.026) and 1.0 MAC (KO: 51+/-6 min(-1), WT: 94+/-6 min(-1), P=0.001). Hypercapnia (5% CO2) increased RR in awake and decreased RR in nesthetized (1.0 MAC) mice, whereby relative changes were larger in AE3 KO mice. Recovery from isoflurane anesthesia in respect to RR regaining baseline values was more pronounced in AE3 KO. Results show that AE3 expression profoundly influences control of breathing in mice.

[Catecholamine-resistant hypotension -- an update]. / Katecholaminrefraktäre Hypotension -- aktuelle Entwicklungen.

Vasoplegia as catecholamine resistent hypotension occurs in severe hemorrhagic or septic shock and post cardiopulmonary bypass. The entire rational behind this phenomenon is still unclear. An ATP-shortage in the vascular musculature, disregulation of vasopressin release, and the activation of ATP-dependent potassium-channels are discussed. In the last years, attention is drawn towards the activation of ATP-dependent potassium-channels and the possible therapeutic inhibition by glibenclamid. However, inhibition of potassium-channels does not normalize blood pressure under all circumstances. In particular in septic shock other mechanisms have to be involved. Overall, the sometimes desperate clinical situation has led to a large number of case reports und uncontrolled series of retrospectively analysed cases, where vasopressin or methylenblue were discribed as successfully reversing catecholamine resistent hypotension. Nevertheless, in hemorrhagic and septic shock scientific evidence of the clinical effects and the right dose as well as placebo controlled studies comparing the agents and possible combinations of agents are desirable but hardly available yet. In the case of severe hypotension following surgery under cardiopulmonary bypass results of the first randomized and placebo controlled studies describe successful restoration of blood pressure and even a decrease in perioperative mortality. Concerning the side effects, vasopressin and methylenblue, like most vasopressors, can cause gastrointestinal ischemia, but with the small number of patients enrolled so far, further major side effects can not be ruled out. Accordingly, the identification of risk factors for the development of vasoplegia and the prediction of the extent of the response or the rate of non-responders to these treatments are widely unknown. However, although the administration of vasopressin and methylenblue can not be recommended as a standard treatment it provides an additional option in individual cases of life threatening vasoplegia.