The Effects of Volatile Anesthetics on Renal Sympathetic and Phrenic Nerve Activity during Acute Intermittent Hypoxia in Rats.

Coordinated activation of sympathetic and respiratory nervous systems is crucial in responses to noxious stimuli such as intermittent hypoxia. Acute intermittent hypoxia (AIH) is a valuable model for studying obstructive sleep apnea (OSA) pathophysiology, and stimulation of breathing during AIH is known to elicit long-term changes in respiratory and sympathetic functions. The aim of this study was to record the renal sympathetic nerve activity (RSNA) and phrenic nerve activity (PNA) during the AIH protocol in rats exposed to monoanesthesia with sevoflurane or isoflurane. Adult male Sprague-Dawley rats (n = 24; weight: 280-360 g) were selected and randomly divided into three groups: two experimental groups (sevoflurane group, n = 6; isoflurane group, n = 6) and a control group (urethane group, n = 12). The AIH protocol was identical in all studied groups and consisted in delivering five 3 min-long hypoxic episodes (fraction of inspired oxygen, FiO2 = 0.09), separated by 3 min recovery intervals at FiO2 = 0.5. Volatile anesthetics, isoflurane and sevoflurane, blunted the RSNA response to AIH in comparison to urethane anesthesia. Additionally, the PNA response to acute intermittent hypoxia was preserved, indicating that the respiratory system might be more robust than the sympathetic system response during exposure to acute intermittent hypoxia.

Longitudinal assessment of preoperative dexamethasone administration on cognitive function after cardiac surgery: a 4-year follow-up of a randomized controlled trial.

BACKGROUND: The pathogenesis of postoperative cognitive decline (POCD) is still poorly understood; however, the inflammatory response to surgical procedures seems likely to be involved. In addition, our recent randomized controlled trial showed that perioperative corticosteroid treatment may ameliorate early POCD after cardiac surgery. To assess the long-term effect of dexamethasone administration on cognitive function, we conducted a 4-year follow-up. METHODS: The patients were randomized to receive a single intravenous bolus of 0.1 mg kg- 1 dexamethasone or placebo 10 h before elective cardiac surgery. The endpoint in both groups was POCD incidence on the 6th day and four years postoperatively. RESULTS: Of the 161 patients analyzed previously, the current follow-up included 116 patients. Compared to the 62 patients in the placebo group, the 54 patients in the dexamethasone group showed a lower incidence of POCD on the 6th day (relative risk (RR), 0.510; 95 % confidence interval (CI), 0.241 to 1.079; p = 0.067, time interval also analyzed previously) and four years (RR, 0.459; 95 % CI, 0.192 to 1.100; p = 0.068) after cardiac surgery. The change in cognitive status between the two postoperative measurements was not significant (p = 0.010) among the patients in the dexamethasone group, in contrast to patients in the placebo group (p = 0.673). CONCLUSIONS: Although statistical significance was not reached in the current study, the prophylactic administration of dexamethasone seems to be useful to prevent POCD development following cardiac surgery. However, further large multicenter research is needed to confirm these directions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02767713 (10/05/2016).

Increase of plasma S100B and neuron-specific enolase in children following adenotonsillectomy: a prospective clinical trial.

S100B protein and neuron-specific enolase (NSE) can be considered the markers of cerebral injury. To our knowledge the association of general anesthesia for elective non-cardiac surgery in children with these markers has not been studied before. The goal of this study was to find out whether these markers change after adenotonsillectomy with general anesthesia. The secondary goal was to determine whether different types of anesthesia, gender, age and body mass index are associated with the change of S100B and NSE after adenotonsillectomy with general anesthesia. This study was designed as a prospective clinical trial. We did a simple pre-post experiment with no control group. In 59 children (aged 6-13, ASA I-II) undergoing adenotonsillectomy and randomized to TIVA or inhalational general anesthesia, plasma S100B and NSE were measured during anesthesia before and after the surgery which lasted a median (interquartile range) of 16.5 (13.0-20.0) min. S100B and NSE assays were performed using the electrochemiluminescence immunoassay. Significance of the differences was assessed by two-tailed asymptotic Wilcoxon signed rank test. Main outcome measures were differences in the levels of S100B and NSE before and after the general anesthesia and surgery. There were significant increases in S100B and NSE levels after the surgery. S100B was increased by 38% (P < 0.001) and NSE was increased by 10% (P < 0.001). Increase of S100B was significantly negatively associated with age (P = 0.023). We have not found significant association of S100B and NSE with any other of the monitored variables. The values of neurological biomarkers S100B and NSE were significantly increased after general anesthesia for elective adenotonsillectomy in children.

Are postoperative behavioural changes after adenotonsillectomy in children influenced by the type of anaesthesia?: A randomised clinical study.

BACKGROUND: Negative postoperative behavioural changes (NPOBCs) are very frequent in children after surgery and general anaesthesia. If they persist, emotional and cognitive development may be affected significantly. OBJECTIVE: To assess whether the choice of different anaesthetic techniques for adenotonsillectomy may impact upon the incidence of NPOBC in repeated measurements. DESIGN: A randomised, controlled, parallel-group trial. SETTING: University Hospital Split, Croatia. PATIENTS: Sixty-four children (aged 6 to 12 years, ASA 1 to 2) undergoing adenotonsillectomy assigned into one of two groups: sevoflurane (S) (n = 32) or total intravenous anaesthesia (TIVA) (n = 32). INTERVENTIONS: Permuted-block randomisation with random block sizes of 4, 6 and 8, administering anaesthesia, and evaluation of NPOBC with the Post Hospitalization Behavior Questionnaire (PHBQ: 27 items describing six subscales). The PHBQ was filled out by parents at postoperative days (POD) 1, 3, 7 and 14, and 6 months after surgery. MAIN OUTCOME MEASURES: Differences in numbers of NPOBCs between two anaesthesia techniques, and NPOBC analysis by subscales. RESULTS: The prevalence of at least one NPOBC after surgery ranged from a maximum of 80% [95% confidence interval (CI) 71 to 90%] on POD 1 to a minimum of 43% (95% CI 31 to 56%) 6 months after surgery. Absolute risk reduction for at least one NPOBC in the TIVA group compared with the S group increased from 0.24 on POD 1 to 0.55 6 months after surgery. The number of NPOBCs was also lower in the TIVA group [median 5, interquartile range (IQR) 2 to 10] than in the S group (median 22, IQR 10 to 32) (P < 0.001). The overall number of NPOBCs within PHBQ subscales was significantly lower in the TIVA group than in the S group. The largest difference in the number of NPOBCs between groups was observed for the separation anxiety subscale (mean 5, 95% CI 1 to 9; P < 0.001) followed by the general anxiety subscale (mean 4, 95% CI 3 to 5; P < 0.001) and apathy/withdrawal subscale (mean 3, 95% CI 1 to 5; P < 0.001). CONCLUSION: The prevalence of NPOBC after elective adenotonsillectomy in 6 to 12-year-old children was very high (80%). The choice of anaesthetic technique for adenotonsillectomy in children influenced the incidence and type of NPOBC. Sevoflurane/nitrous oxide anaesthesia was associated with more frequent and prolonged NPOBCs than TIVA, especially in the separation anxiety, general anxiety and withdrawal/apathy subscales.

Sevoflurane and isoflurane monoanesthesia abolished the phrenic long-term facilitation in rats.

Phrenic long-term facilitation (pLTF) is a form of respiratory plasticity, manifested by prolonged increase in peak amplitude of phrenic nerve activity (PNA) after episodes of acute intermittent hypoxia (AIH). The aim was to investigate the effects of sevoflurane and isoflurane monoanesthesia at equipotent anesthetic doses on the expression of amplitude pLTF. Experiments were performed on Sprague-Dawley anesthetized, vagotomized, and mechanically ventilated rats. Two experimental groups, sevoflurane and isoflurane, and a control group (urethane-anesthetized) were formed. Peak amplitude of phrenic nerve activity, respiratory frequency and breathing rhythm parameters (Ti, inspiratory duration; Te, expiratory duration; and Ttot, total respiratory time duration) were analyzed during hypoxic episodes, and at 15, 30, and 60min after the last hypoxic episode. In the control group average PNA increased by 173.03±70.16% (p<0.001), at 60min after the last hypoxic episode compared to baseline values. Therefore amplitude pLTF was induced. In the sevoflurane and isoflurane groups PNA failed to increase, and in fact decreased by 15.79±15.18% and 31.00±11.00%, respectively (p>0.05). Amplitude pLTF was abolished during sevoflurane and isoflurane monoanesthesia.

Blood pressure dipping and salivary cortisol as markers of fatigue and sleep deprivation in staff anesthesiologists.

Anesthesiologists often work extended duty shifts that result in acute and chronic sleep loss and circadian disruption. Stress caused by sleep deprivation, together with excessive workload could contribute to acute increases in blood pressure (BP) and sympathetic nervous system activity. Non-dipping pattern of BP is considered an additional risk factor for cardiovascular events and target organ damage. We hypothesized that there would be significant changes of cardiovascular parameters when comparing work on call during the 24-hour in-hospital shift (24-HD) versus ordinary working day (8-HD) combined with changes of dipping pattern and altered diurnal cortisol secretion, measured by salivary cortisol (SC). Following local Medical Ethics Committee approval, 12 out of 36 staff anesthesiologists (8 male, 4 female), 33-61 years old, participated in this study. Ambulatory BP monitor was used for noninvasive 24-hour ambulatory BP and heart rate (HR) monitoring. Each participant was monitored continuously during the 8-HD, as well as during the 24-HD. Saliva for analysis of cortisol levels was collected six times a day (at 8 am, 11 am, 2 pm, 5pm, 8pm, and 11 pm) both during 8-HD and on 24-HD. There was a significant decrease in number of diastolic dippers on call vs. diastolic dippers on ordinary working day (4/12 vs. 10/12, p=0.036), and non significant decrease of systolic dippers (3/12 vs. 7/12, p =0.214). There were no significant differences in SC values between 8-HD and 24-HD at all observed time points. However, the SC values measured during the night were markedly elevated on both days compared with reference values and the shapes of SC curves were altered. The lack of diastolic BP dipping could be more sensitive indicator of stress among staff anesthesiologists than systolic BP dipping. The shape of SC diurnal curve in terms of elevated night values could be another indicator of their chronic fatigue.

Succinylcholine use in adult anesthesia - A multinational questionnaire survey.

There are no definitive evidence based standards regarding use of succinylcholine (SCh) for anesthesia induction. However, there is a global trend toward eliminating SCh not only in elective, but also in emergency surgery in adults. The aim of the study was to survey the use of SCh in adult elective and emergency anesthesia practice in several European countries and the United States by questionnaire. One hundred and seventy anesthesiologists out of 201 possible, from six institutions in five countries (Croatia, Bosnia and Herzegovina, Hungary, United Kingdom, and the United States) anonymously completed the questionnaire about their use of SCh. The questionnaire was structured to assess the respondents': frequency of use of SCh in adult surgery (elective and emergency), reasons for use or rejection of SCh, positive and negative attributes of SCh, and observed side effects in their practice. Differences in use were tested using X2-test when appropriate. There was a significant difference in the use of SCh between countries for elective surgery with the lower use in UK and Hungary (chi2=45.8, p <0.001). One hundred and seventeen (69%) use it regularly. In emergency surgery 165 (97%) anesthesiologists use it without any significant difference among countries (chi2=2.13, p<0.711). The top indications for SCh use were anticipated difficult intubation/ventilation (74%), caesarean section (54%), and obesity and/or hiatus hernia (49%). The top reasons against SCh use were adequate substitutes (87%), fear of arrhythmias (45%), and anaphylaxis (19%). The most desirable reported drug features were: rapid onset (88%), short duration (64%), and effective relaxation (61%). Forty-six per cent of the surveyed anesthesiologists stated they had never experienced a complication with its use. The most frequently reported side effects were myalgias (47%), bradycardias (42%), and prolonged blockade (39%). Allergic reactions were reported by 13%, and asystole by 12% of physicians. From our survey it is possible to conclude that succinylcholine is still regularly used, at least by surveyed anesthesiologists in Europe and USA, in adult anesthesia practice, especially in elective surgery for which it may be least suited. This reflects the discrepancies between the international guidelines for the use of SCh and the clinical practice of many anesthesiologists in different countries. The regional differences in SCh usage may be considered through anesthesia cultures and practice variations depending on country.

Combined usage of inhaled and intravenous milrinone in pulmonary hypertension after heart valve surgery.

Secondary pulmonary hypertension is a frequent condition after heart valve surgery. It may significantly complicate the perioperative management and increase patients' morbidity and mortality. The treatment has not been yet completely defined principally because of lack of the selectivity of drugs for the pulmonary vasculature. The usage of inhaled milrinone could be the possible therapeutic option. Inodilator milrinone is commonly used intravenously for patients with pulmonary hypertension and ventricular dysfunction in cardiac surgery. The decrease in systemic vascular resistance frequently necessitates concomitant use of norepinephrine. Pulmonary vasodilators might be more effective and also devoid of potentially dangerous systemic side effects if applied by inhalation, thus acting predominantly on pulmonary circulation. There are only few reports of inhaled milrinone usage in adult post cardiac surgical patients. We reported 2 patients with severe pulmonary hypertension after valve surgery. Because of desperate clinical situation, we decided to use the combination of inhaled and intravenous milrinone. Inhaled milrinone was delivered by means of pneumatic medication nebulizer dissolved with saline in final concentration of 0.5 mg/ml. The nebulizer was attached to the inspiratory limb of the ventilator circuit, just before the Y-piece. We obtained satisfactory reduction in mean pulmonary artery pressure in both patients, and they were successfully extubated and discharged. Although it is a very small sample of patients, we conclude that the combination of inhaled and intravenous milrinone could be an effective treatment of secondary pulmonary hypertension in high-risk cardiac valve surgery patient. The exact indications for inhaled milrinone usage, optimal concentrations for this route, and the beginning and duration of treatment are yet to be determined.

[Succinylcholine use by anesthesiologists in Croatia--is it really abandoned?]. / Uporaba sukcinil-kolina medu hrvatskim anesteziolozima--je li taj lijek zaista odbacen?

The aim was to establish the prevalence of succinylcholine use among Croatian anesthesiologists in adult elective and emergency surgery, as well as in pediatric surgery, regarding gender, position, working place, and working experience of physicians. The anesthesiologists were expected to express their personal opinions regarding the drug, as well as experienced side effects in their own clinical practice. A total of 125 anesthesiologists (out of 590 in Croatia) from both university and county hospitals in Croatia anonymously filled out the questionnaire regarding the use of succinylcholine (Appendix 1). The questionnaire was structured to assess the use of succinylcholine in adult elective and emergency surgery, and in pediatric anesthesia, to obtain the reasons for the preference or rejection of succinylcholine, and information about observed side effects. The differences in use regarding gender, position, working place, and working experience were tested using chi-squared test and Fisher's exact test. p < 0.05 was considered significant. Vast majority (approximately 70%) of anesthesiologists in Croatia still use succinylcholine. The percentages of anesthesiologists that never use succinylcholine in adult elective, adult emergency and pediatric surgery were 20%, 6%, and 31%, respectively. There were no significant differences in the use of succinylcholine regarding position, working place, and working experience, but male anesthesiologists used it less frequently in pediatric anesthesia compared with their female colleagues (chi2 = 5.08; p = 0.02). Forty-two per cent never experienced a complication from the drug use. The most frequently reported side effects were bradycardias (67%) and myalgias (54%), followed by prolonged blockade (33%), and allergy (33%). Asystole was reported by 10% of the respondents. In conclusion, succinylcholine is still widely used by anesthesiologists in Croatia. The majority of surveyed physicians were aware of its possible dangerous adverse effects, but still use it in certain situations. Therefore, indications and contraindications for its use deserve expert consensus guidelines based on the available scientific evidence.

The impact of a single 24 h working day on cognitive and psychomotor performance in staff anaesthesiologists.

BACKGROUND AND OBJECTIVE: The profession of anaesthesiologist is demanding and potentially hazardous. Extended work shifts combined with intensive work load may adversely affect physicians' performance. The aim of this study was to explore the impact of a single in-hospital 24 h shift on the cognitive and psychomotor performance of anaesthesiologists in a surgical emergency department. METHODS: Following ethical and institutional approval, 11 staff anaesthesiologists [six men, five women, age 48 (35-50), years of experience 17 (7-20), median (range)] successfully completed the study protocol. Four computer-generated psychological tests (CRD, Complex Reactionmeter Drenovac, Croatia) consisting of light signal position discrimination (CRD 311), simple visual orientation (CRD 21), simple arithmetic operations (CRD 11), and complex psychomotor coordination (CRD 411) were used to measure objective parameters of cognitive and psychomotor performance at four time points (D1 = 8:00 a.m., D2 = 3:00 p.m., D3 = 11:00 p.m.; and D4 = 7:00-8:00 a.m. next day) during the 24 h working day. The control testing on an ordinary working day was performed at two time points (C1 = 8:00 a.m., C2 = 3:00 p.m.). Three parameters were recorded: total test solving time (TTST), total variability, and total number of errors for all four tests. RESULTS: TTST was significantly impaired during the 24 h shift in all tests, and TTST was prolonged in CRD 21 test at different time points from 1.6 +/- 1.4 to 5.5 +/- 1.6 s compared with the control (F = 6.39, P = 0.001). The reaction times were prolonged from 1.3 +/- 1.8 to 5.4 +/- 1.2 s (F = 3.49, P = 0.009) in CRD 311, from 3.8 +/- 9.0 to 34.3 +/- 5.8 s (F = 5.05, P = 0.002) in CRD 11 TTST, and from 0.8 +/- 3.0 to 16.3 +/- 8.6 s (F = 2.67, P = 0.034) in CRD 411. Total variability was significantly altered during the 24 h shift only in CRD 411 (F = 2.63, P = 0.036). There was no difference in the total number of errors between the 24 h shift and the ordinary working day. CONCLUSION: Anaesthesiologists' 24 h working day in the emergency department altered cognitive and psychomotor function in comparison with ordinary working days. Speed, reliability and mental endurance (measured by TTST) were significantly impaired in all four tests. Stability and reaction time (measured by total variability) were only slightly impaired. Paradoxically, attention and alertness (measured by total number of errors) were not adversely affected. In conclusion, anaesthesiologists' psychomotor performance was impaired during the single 24 h shift.

[Sleep disordered breathing]. / Poremecaji disanja tijekom spavanja.

Sleep apnea is a breathing disorder characterized by cessation of breathing during sleep, oxygen desaturation and awakenings during night. There are several types of breathing disorders during sleep. Obstructive sleep apnea (OSA) is also characterized by snoring and excessive daytime sleepiness. Central sleep apnea (CSA) is less common and characterized by reduced respiratory drive from the central nervous system. Upper airway resistance syndrome (UARS) is characterized by excessive daytime sleepiness, absence ofapneas, hypopneas and lack of significant oxygen desaturation. The consequences of the abnormal breathing during sleep include excessive daytime sleepiness, development of arterial hypertension, ischemic cardiac disease, neurocognitive dysfunction, glaucomic optico-neuropathy, metabolic dysfunction. The early diagnosis requires detailed anamnestic data, standardized questionnaires for detection of sleep disordered breathing and whole-night polysomnography in the sleep laboratory. Obstructive sleep apnea can be treated with continuous positive airway pressure (CPAP), oral appliances, and surgery (e.g., uvulopalatopharyngoplasty, UPPP). Early diagnosis of OSA enables early treatment, improvement of its symptoms and eventually reduces development of co-morbidities.

[Obstructive sleep apnea and anesthesia]. / Opstrukcijska apneja tijekom spavanja i anestezija.

Even though the effects of surgery and anesthesia on sleep have not been completely defined yet, it is an irrefutable fact that the patients with sleep apnea could experience significant perioperative complications, in terms of common difficult airway problems, as well as prolonged emergence from anesthesia. Besides, there are strong evidences of correlation between sleep apnea and hypertension and other cardiovascular diseases. Preoperative questions about sleep, possible snoring, or excessive daytime sleepiness should become a routine part of preanesthesia evaluation, together with airway examination and thorough pulmonary and cardiovacular examination. However, the exact severity of the obstructive sleep apnea (OSA) could be precisely defined only by polysomnography. Every patient diagnosed with OSA, or with clinical suspicion of OSA, should be considered to have a difficult airway, until proven otherwise, and consequently has increased risk of anesthesia. The possible problems may arise during tracheal intubation, extubation, or with postoperative analgesia, since opioids increase the incidence of pharyngeal collapse. Whenever possible, regional anesthesia techniques should be used. On the other hand, by documenting every difficult airway management, difficult intubation or prolonged recovery, the anesthesiologists are in good position to effectively screen for OSA in population.

Association of oculocardiac reflex and postoperative nausea and vomiting in strabismus surgery in children anesthetized with halothane and nitrous oxide.

BACKGROUND: Postoperative nausea and vomiting (PONV) occurs frequently after strabismus surgery. The controversy still exists regarding the association of PONV and the oculocardiac reflex (OCR). A recent study has proven that rocuronium attenuates OCR. If these two occurrences are dependent, it is expected that with the diminution of OCR, occurrence of PONV will also be reduced. The goal of this randomized, controlled study was to prove an association between OCR and PONV by attenuating OCR with 0.4 mg x kg(-1) of rocuronium and subsequently diminishing PONV if these occurrences are associated. METHODS: A total of 119 ASA 1 children, aged between 3 and 10, undergoing surgery of the medial rectus muscle, were randomly assigned to two groups. In group R (n = 59), 0.4 mg x kg(-1) of rocuronium was administered i.v. before intubation. Group C (controls, n = 60) received no muscle relaxant. The anesthesia was induced and maintained with halothane and N(2)O/O(2) (50/50%). Chi-squared test, Fisher's exact test, t-test, and anova were used for statistical analysis; P-value <0.05 was considered statistically significant. RESULTS: There were no differences between groups regarding patients' characteristics as well as endtidal halothane and duration of surgery and anesthesia. The occurrence of OCR was different between groups (R: 16/59, 27.1%, C: 28/60, 46.7%; P = 0.027), but not the occurrence of PONV (R: 27/59, 45.8%, C: 28/60, 46.7%; P = 0.921). There was an equal number of patients with PONV and bradycardias in both groups (R: 4/27 vs C: 4/28; P = 0.858), whereas there was different, but statistically insignificant distribution of patients (R: 3/27 vs C: 10/28; P = 0.086) with PONV and arrhythmias other than bradycardia. However, simultaneous occurrence of total OCR and PONV in the 24-h period was not different between the two groups (P = 0.964). CONCLUSIONS: Rocuronium (0.4 mg x kg(-1)) attenuates the occurrence of OCR, but with the reduced occurrence of OCR we were not able to attenuate the occurrence of PONV, therefore the association of OCR and PONV in strabismus surgery in children anesthetized with halothane and nitrous oxide remains unclear, and if there is a link between the two, it could be related to arrhythmias and not bradycardia.