A year in review in Minerva Anestesiologica 2012

COPYRIGHT 2013 EDIZIONI MINERVA MEDICA Y E A R I N R E V I E W A year in review in Minerva Anestesiologica 2012 D. CHIUMELLO 1, M. ALLEGRI 2, F. CAVALIERE 3, G. DE COSMO 3 G. IOHOM 4, O. LANGERON 5, D. PIETRINI 3, M. ROSSI 6 1Dipartimento di Anestesia, Rianimazione (Intensiva e Subintensiva) e Terapia del Dolore, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milano, Italia; 2Department of Surgical Clinical Diagnostic and Pediatric Science, Pain fterapy Service, University of Pavia-Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 3Istituto di Anestesia e Rianimazione, Università Cattolica Sacro Cuore, Policlinico “A. Gemelli”, Roma, Italia; 4Department of Anesthesia and Intensive Care Medicine, Cork University Hospital and University College Cork, Wilton, Cork, Ireland; 5Department of Anesthesiology and Intensive Care, Hôpital de la Pitié-Salpêtrière, Paris, France; 6Dipartimento di Anestesia, Terapia Intensiva e Terapia del Dolore, Centro di ricerche e formazione ad Alta Tecnologica nelle Scienze Biomediche “San Giovanni Paolo II”, Università Cattolica Sacro Cuore, Campobasso, Italia General anesthesia he analysis of electroencephalogram (EEG) signal is of the outmost importance in the perioperative period. It is indeed useful to evalu- ate the depth of anesthesia, particularly when muscle relaxant are used; to point out early al- terations of cerebral metabolism due to hypoxia or ischemia, such as during carotid surgery; to diagnose seizure disorders; and to titrate drugs in pharmacologically-induced coma.1 Gross EEG abnormalities (absence of electrical activ- ity, burst suppression) are immediately apparent even to non-specialists, but subtle pronounced changes are more difficult to detect. For this rea- son, some computerized systems are now avail- able that process EEG signals and provide anes- thetists with numeric scores informative of the depth of anesthesia.2 As each system is based on its own mathematical algorithm, the usefulness of these indices should be tested by comparison with clinical data and with scores provided by other systems. Pilge et al. challenged two wide- spread devices (BIS A-2000 and Cerebral State monitors) with the same EEG signals previously recorded in a group of patients under general an- esthesia.3 ftey showed that, although the scores provided by the two devices correlated well (r=0.68), depth of anesthesia was similar in only 51% of cases and the scores differed by more than 10 points in over 40% of cases. fte authors hypothesized that such inconsistencies might originate from different latencies in recording EEG changes. Interestingly, the inconsistencies were greater during sevoflurane anesthesia com- pared to propofol anesthesia. ftis finding sug- gests that the two anesthetics may affect EEG differently or that the cerebral state index algo- rithm is less effective when applied to sevoflu- rane anesthesia because it was developed from a database recorded during propofol anesthesia.3 During extracranial carotid surgery, shunt- ing is sometimes necessary to prevent cerebral ischemia, although it increases the complexity of the procedure. fte decision of placing a shunt is taken immediately after clamping the carotid ar- tery on the basis of clinical, hemodynamic, and instrumental data. If the procedure is performed in awake patients under regional anesthesia, cerebral hypoperfusion is promptly detected by neurological evaluation. If the patient is under general anesthesia, trans-cranial cerebral oxym- etry (TCCO) can help to detect cerebral hypop- erfusion.4 To verify the effectiveness of TCCO, Stilo et al. compared the information collected by neurological examination (considered the gold standard) with that obtained by TCCO in a series of 100 patients who underwent carotid surgery under local anesthesia.5 fte decision of COPYRIGHT 2013 EDIZIONI MINERVA MEDICA A yEAR IN REVIEW IN MINERVA ANESTESIOLOGICA 2012 CHIUMELLO placing a shunt was taken on the basis of neu- rological examination and it was assumed that a TCCO fall of more than 20% would have requested shunting in a procedure carried out under general anesthesia. In patients included in the study, TCCO data were poorly predictive of neurological evaluation. Messerer et al. published an exhaustive review on neuromonitoring techniques following major neurosurgical procedures.6 fte authors exam- ined both invasive and non invasive methods, re- ported their indications, and discussed the ‘pros’ and ‘cons’ of each. Prevention of pulmonary atelectasis is one of the major challenges of mechanical ventilation in the perioperative period. fte expiratory flow limitation (EFL) is a phenomenon that often precedes the development of atelectasis.7 EFL is caused by the collapse of bronchioles during ex- piration and it is directly related to the decrease of the functional residual capacity that occurs dur- ing general anesthesia. EFL is important because it impairs alveolar ventilation, favors atelectasis 8 and the periodic opening and closing of small airways which might cause release of inflamma- tory mediators.9 Marangoni et al. investigated EFL during general anesthesia in 52 patients who underwent abdominal surgery.10 Patients were randomly allocated to receive ZEEP or PEEP (5 cmH2O) and the presence of EFL was assessed the day before surgery, after anesthesia induction, and at the end of surgery. fte study showed that the proportion of patients who de- veloped EFL was equal in the two groups follow- ing induction of anesthesia, but much greater in the ZEEP group compared to the PEEP group by the end of surgery. Left ventricle diastolic dysfunction can influ- ence patient course in the perioperative period.11 In particular, diastolic function evaluated by in- traoperative transesophageal echocardiography is useful into predicting outcomes in cardiac patients who undergo cardiac and non cardiac surgery.12 Cabrera Schulmeyer et al. evaluated the left ventricle filling pressure intraoperatively by assessing the E/e’ index derived from tissue Doppler imaging and pulsed Doppler.13 Elevat- ed values of the ratio were associated with greater incidence of postoperative cardiovascular events, pulmonary congestion, arrhythmias, longer ICU and hospital stays. Beds in surgical intensive care units (SICUs) are a very limited resource and their optimal use requires correct triage of surgical patients admit- ted to SICUs, high dependency units (HDUs), or surgical wards. fte Modified Early Warn- ing Score (MWS) has been successfully used to regulate patient admission to medical intensive care units.14, 15 Peris et al. evaluated the effects of adopting a protocol of admission to SICU fol- lowing emergency surgery based on this score.16 fte results of the study showed that after intro- ducing MEWS as the criterion of admission to ICU or HDU following emergency surgery, the proportion of patients admitted to SICU de- creased significantly (5% vs. 11%), whereas the percentage of patients admitted to the HDU in- creased (21% vs. 14%). As perioperative mortal- ity and morbidity were unaffected, the authors concluded that systematic use of MEWS may improve SICU bed allocation. Due to the continuing increase of patients with diabetes mellitus (known and unrecog- nized) physicians are expected to manage a higher number of hyperglycemia events during the perioperative period. Kadoi y reviewed the blood glucose control in the preoperative period and, during anesthesia focusing especially on an- esthetic agents.17 An alternative inhalational anesthesia tech- nique could be performed using the anesthetic conserving device AnaConDa™ (Sedana Medi- cal, Sundbyberg, Sweden). ftis is a single-use device for continuous administration of inhaled anesthetic via a syringe pump. fte AnaConDa™ is a disposable vaporizer enabling the anesthetic agent delivery to the lungs during inspiration. It is connected between the y-piece of the respira- tory circuit and the endotracheal tube, as a heat and moisture exchanger. It requires a syringe pump, anesthetic gas monitor and anesthetic gas scavanging. For general anesthesia using solely sevoflurane in air, an inspiratory concentration above 1.5% is necessary. Nishiyama et al. investi- gated the feasibility of the AnaConDa™ to deliver sevoflurane at 1.5-2% during general anesthesia with a total gas flow of 4 L/min.18 fte authors concluded that AnaConDa™ saved sevoflurane COPYRIGHT 2013 EDIZIONI MINERVA MEDICA CHIUMELLO A yEAR IN REVIEW IN MINERVA ANESTESIOLOGICA 2012 and hastened emergence from anesthesia (8±4 vs. 14±2 min, P<0.05) compared to the conven- tional vaporizer. As Gentili pointed out in his editorial accompanying this study,5 AnaConDa™ could increase the dead space of the respiratory circuit by about 100 mL and as such could affect gas exchange. ftis may result in a higher ETCO2, in patients with pulmonary disease, making nec- essary tidal volume adjustments of 5-10 mL/kg to maintain normocapnia.19 From 2003 to 2007, use of robotic-assisted laparoscopic prostatectomy (RALP) increased from 5.7% to 50.3% of all radical prostatec- tomy.20 Nevertheless, more genitourinary com- plications, incontinence and erectile dysfunction were observed in the robotic-assisted surgical procedure.21 Due to the increased incidence of prostate cancer, and because this incidence is ex- pected to grow every year, RALP posed real an- esthetic concerns, as pointed out by Gainsburg in his review.22 A promising new technology is the brain oxygen monitor based on near infrared spec- troscopy (NIRS). NIRS is a non invasive optical device, using the difference between transmitted and received light, to measure optical attenua- tion related to the total loss of light caused by tissue absorption and scattering.23 Neurologic monitoring in acute brain injury is still a major concern as it lags behind cardiac or respiratory monitoring, in guiding therapeutic strategies aimed at improving outcomes. In acute traumat- ic brain injury, monitoring cerebral perfusion and oxygenation is paramount, in order to pre- vent the main complication, cerebral ischemia. NIRS investigations in this setting were limited with no outcome studies, and often part of mul- timodality monitoring consisting of intracra- nial pressure, flow, temperature and metabolic measurements.23, 24 However, in non traumatic acute brain injury, NIRS seems to be a promising monitoring technique during endovascular neu- roradiologic procedures.25 Changes in rSO2, with greater oscillations, were associated with high risk phases of neuroradiological procedures help- ing in prompt diagnosis of adverse outcomes, mainly by detecting flow reduction and ischemia in cerebral arteries related to microcatheter inser- tion, vasospasm, and/or contrast agent injection. Postoperative cognitive dysfunction (POCD) is a major concern after non-cardiac surgery, par- ticularly as a recent study suggested an associa- tion between one year mortality and POCD at both hospital discharge and at three months.26 More interesting are the long-term (beyond one year) consequences of POCD. Steinmetz et al. from the ISPOCD (International Study of Post- operative Cognitive Dysfunction) group demon- strated in a follow up study with a median of 8.5 years in a cohort of 701 patients, that cognitive dysfunction after noncardiac surgery was associ- ated with increased mortality when POCD was observed at three months. In addition, the risk of leaving the labor market prematurely, or de- pendency on social transfer payments was more likely when a cognitive decline was observed at one week after surgery.27 fte same group as- sessed the hypothesis of association between POCD occurrence after propofol anesthesia and various phenotypes owing to polymorphisms in cytochrome P450 encoding genes (CyP genes).28 In 337 patients with a median age of 67 years included in this study, POCD was observed in 9.4% and 7.8% at one week and three months respectively. None of the examined CyP alleles or phenotypes were associated with POCD.28 fte authors concluded that polymorphism in CyP genes were not associated with POCD oc- currence after noncardiac surgery in patients an- esthetized with propofol. ftese results support the assumption that POCD has a multifactorial origin, including several risk factors such as older age, specific CyP polymorphisms and adminis- tered drugs.29, 28 In this context, evaluation of perioperative risk in elderly patients is a key issue. Aubrun et al. in a review, emphasized that aging is charac- terized by limited organ reserve. ftus potential organ failure in response to perioperative stress makes maintenance of homeostasis more diffi- cult in older people.30 ftis greater vulnerability is associated with higher perioperative morbid- ity and mortality. Hypertension and dyspnea are the two most prominent risk factors for postop- erative complications in the elderly. In addition, unrelieved or undertreated pain is frequent and may have adverse consequences in this patient population.30 COPYRIGHT 2013 EDIZIONI MINERVA MEDICA A yEAR IN REVIEW IN MINERVA ANESTESIOLOGICA 2012 CHIUMELLO Pharmacological agents Recombinant active factor VII (rFVIIa) is ap- proved for the treatment of bleeding in hemo- philiacs with antibodies to factors VIII or IX, and in other coagulopathies such as factor VII deficiency, acquired von Willebrand’s disease, thrombocytopenia, and platelet function disor- ders.31 It has also been reported to reduce surgi- cal bleeding during retropubic prostatectomy, in the absence of coagulopathy.32 Moreover, consensus guidelines support the use of rFVIIa, as an adjunct to the surgical con- trol of bleeding, in the management of massive hemorrhage due to blunt trauma.33 Imberti et al. evaluated intraoperative intrave- nous administration of rFVIIa during early evac- uation of spontaneous intracerebral hematoma (ICH).34 fte purpose of this study was to assess if administration of rFVIIa as described prevents postoperative rebleeding. fte authors reported that rFVIIa did not influence hematoma forma- tion following early ICH surgery, and that po- tential benefit of rFVIIa administration may be demonstrated in a larger study.34 Survey Della Rocca et al. reported the results of a survey on the use of neuromuscular blocking agents, carried out on a large sample of Italian anesthetists (N.=1440).35 fte authors focused the questionnaire on the recovery from muscular block. Among the wealth of information col- lected, they found that about 50% of the sur- veyed anesthetists relied solely on clinical tests (sustained head lift, eye opening, etc.) to evalu- ate the degree of recovery from the block at the end of surgery. fte authors speculated that such habit may be explained by the limited availabil- ity of neuromuscular monitoring systems. Dong et al. reported the results of a survey on hypersensitivity reactions during anesthesia that occurred in France between 2005-2007.36 Data on 1253 cases were analyzed to investigate epidemiology, which drugs were more frequently incriminated, and which tests were commonly employed for diagnosis. Results showed that fe- males were more frequently affected than males (70% of total) and that neuromuscular block- ing agents (NMBA), latex, and antibiotics were responsible of about 85% of anaphylaxis cases. Among NMBA, succinylcholine was the cause in 69% of cases, followed by atracurium (20%). Regional anesthesia Adequate intraoperative anesthesia and post- operative analgesia remain challenging for an- esthetists. Recent years have seen an explosion of locoregional anesthesia techniques due to proven benefits such as less postoperative pain, less postoperative complications, shorter hospi- tal stay and faster postoperative recovery. fte greater number of loco-regional techniques was due initially to the introduction of nerve stimu- lator techniques and later that of ultrasound for plexus and peripheral nerve blocks, as pointed by Jakobsson.37 Di Filippo et al. in their study found that iden- tification of nerves by means of ultrasounds may result not only in improved patient safety but also in an increased success rate. Two hundred and two consecutive patients undergoing infra- clavicular block by ultrasound technique, were enrolled. fte arrangement of the three cords was highly variable around the artery. In a small but significant percentage of patients (8.9%) the me- dial and the lateral cords were located together at the top of the artery. fte position of the vein respective to the artery and nerves was markedly variable.38 Other strategies used to improve quality, dura- tion of anesthesia and post-operative pain relief in patients undergoing plexus block are the addi- tion of adjuvants to the local anesthetic solution. Alemanno et al. evaluated the efficacy of tramadol 1.5 mg/kg as an adjuvant to the local anesthetic solution 0.4 mL/kg of 0.5% levobupivacaine in 40 subjects undergoing shoulder arthroscopy for rotator cuff tear under middle interscalene block. Patients in the “Placebo group” received 0.4 mL/kg 0.5% levobupivacaine plus isotonic sodium chloride perineurally and isotonic so- dium chloride intramuscularly. Patients in the “Perineural tramadol” group received 0.4 ml/ Kg 0.5% levobupivacaine plus 1.5 mg/kg trama- dol perineurally and isotonic sodium chloride COPYRIGHT 2013 EDIZIONI MINERVA MEDICA CHIUMELLO A yEAR IN REVIEW IN MINERVA ANESTESIOLOGICA 2012 intramuscularly. Patients in the “Intramuscu- lar tramadol” group received 0.4 ml/Kg 0.5% levobupivacaine plus isotonic sodium chloride perineurally and 1.5 mg/kg tramadol intramus- cularly. No difference in onset time was detect- ed. Patients who received tramadol added to the local anesthetic solution demonstrated a signifi- cant increase in duration and quality of analgesia without increase of side effects.39 Spinal anesthesia remains a worthwhile tech- nique in many circumstances, including pedi- atric patients; it is an useful alternative to gen- eral anesthesia. fte major concern regarding general anesthesia is the volatile anesthetic that may have negative effects on the development of brain cells and may result in postoperative apnea in ex-premature infants. Although the incidence of apneic episodes is variable, overnight obser- vation after inguinal hernia repair is generally recommended in patients born before 37 weeks gestation who are under 50 weeks post-concep- tual age.40 Lòpez et al. reviewed the indications, contraindications, anatomical and physiological considerations as well as techniques, drugs, dos- ages and complications of spinal anesthesia in pediatric patients. Although considered safe and effective in pediatric patients, spinal anesthesia remains relatively underutilized compared to general anesthesia. fte introduction of ultra- sound is encouraging in this setting.41 Spinal anesthesia is the technique of choice for cesarean section. However, maternal hypoten- sion following spinal anesthesia is a major con- cern because it is frequent and occurs despite low doses of local anesthetic. Hwang et al. in their randomized controlled study of patients under- going caesarean section investigated if prolonged lateral position could reduce hypotension due to sympathetic block and aortocaval compression following spinal anesthesia.42 No difference was found between the two groups regarding to inci- dence of hypotension and ephedrine use. How- ever, difference in onset time of sensory block, level of block and umbilical pH and PCO2 was found. fte conclusion is that maintaining the lateral position is not useful for reducing mater- nal hypotension. In addition, it delays the on- set of sensory block. Scheiermann et al. in the accompanying editorial, commented that the more cephalic spread of the hyperbaric local an- esthetic reported in patient in the lateral position (up to C8) might cause considerable discomfort to the parturient by impairing normal respira- tion and alerts the clinician to the risk of a total spinal anesthesia.43 Another well known and frequently used technique is the lumbar plexus block for lower limb orthopedic surgery. fte lumbar plexus is generally situated within the substance of the psoas major muscle and 2-3 cm deep to the transverse process for which is not easily visible with ultrasound in obese patients. fterefore the skin landmarks are fundamental for its success- ful performance. Most commonly the needle is inserted at the junction of the lateral third and medial two third of a line between the spinous process of L4 and a line passing through the posterior superior iliac spine; hence the need to identify correctly the L4 -L5 in order to target the psoas compartment. Borghi et al. reported that the classical approach (Chayen’s aprroach) which uses the bi-iliac crest as landmark for the L4-L5 interspace is not reliable particularly in obese patients.44 fterefore, a new landmark has been proposed: the soft tissue depression at the prominence of the iliac crest. Two groups have been compared with regards to the easi- ness of performing a lumbar block using the old (Chayen) and the new (Borghi) landmarks. Performance time and the number of needle re- directions needed to obtain an effective block have been evaluated. fte mean time to perform the lumbar plexus block was statistically differ- ent but not clinically relevant. However, when comparing normal weight patients and patients with BMI>30 Kg/m2, the mean block perform- ance time in obese patients was both statistically and clinically different (10.5 min for Chayen’s approach vs. 4.8 min for Borghi’s approach). In conclusion, the new landmark offers several advantages in obese patients as it reduces the number or needle redirections and, most impor- tantly, the failure rate of the block. Regional anesthesia is often associated to general anesthesia in order to decrease the re- sponse to surgical stimuli such that anesthetic consumption and adverse effects can be also de- creased.45 Tsuchiya et al. evaluated the effects of COPYRIGHT 2013 EDIZIONI MINERVA MEDICA A yEAR IN REVIEW IN MINERVA ANESTESIOLOGICA 2012 CHIUMELLO associating transversus abdominal plane block to general anesthesia in 33 ASA III cardiac patients undergoing abdominal surgery.46 ftey found that performing the block decreased anesthetic consumption, shortened anesthesia emergency time, increased intraoperative hemodynamic stability, and decreased the need for vasopressors. Airway management fte role of simulation training for fiberoptic intubation was discussed by Giglioli et al. An- esthesia residents without experience of fiberop- tic intubation were randomly assigned to two groups.47 All residents received an institutional didactic teaching lesson but only 11 subjects had the opportunity to practice on the virtual fiberoptic intubation (VFI) software for one week. Finally, each resident was assessed on the first oro- and nasotracheal intubation on a man- nequin head. fte results showed that self-direct- ed practice using VFI may improve the initial acquisition of fiberoptic intubation skills in an- esthesia residents. In an observational prospective study Falcet- ta et al. enrolled five anesthetists with different levels of experience. ftey were asked to use the Bonfils rigid fiberscope for a six month period.48 Patients undergoing general anesthesia were en- rolled while those with various clinical indicators of a possible difficult intubation were excluded. Direct laringoscopy was performed with a Mac- intosh blade in order to assign a Cormack and Lehane grade prior to proceeding with the Bon- fils rigid fiberscope. While intubating the patient with the Bonfils fiberscope, intubation time and complications were noted. Out of the 216 pa- tients enrolled, three failed intubation were re- corded. Data showed that the learning curve improved significantly after 20 intubations and was affected by the operator’s experience and ap- titude with endoscopic viewing. In conclusion, the Bonfils fiberscope appears to be an efficient, easy to use and safe device for tracheal intuba- tion. In the accompanying editorial Merli G ex- plores ways to improve airway management in general and tracheal intubation in particular.49 Although different intubation techniques have been progressively introduced, adequately pow- ered studies using optical instruments are still lacking. Ilies et al. included 24 patients into a feasibil- ity study; the mean age of the children was 27 months.50 fte authors evaluated Cormack and Lehane (C&L) grade using a Macintosh blade while the intubation was performed using the Glidescope Cobalt. Number of attempts, time to intubation, C&L grade and a subjective score were noted for both a resident and an attend- ing anesthetist. fte authors concluded that the Glidescope proved suitable for use in children. C&L grade was significantly improved in all pa- tients with C&L grade of 2 or 3. fteiler et al. distributed a questionnaire dur- ing the main session of three Anesthesia Meet- ings in Austria (A), the United Kingdom (UK), and Switzerland (CH).51 Questions related to whether anesthetists routinely check for risk fac- tors associated with difficult mask ventilation; whether they routinely mask ventilate prior to administering neuromuscular blocking drugs; whether they apply cricoid pressure. ftis study demonstrated that only a minority of anesthe- siologists checked for all known predictors of difficult mask ventilation prior to anesthesia induction. UK anesthetists’ approach to airway management differed greatly from those in A and CH. Song et al. enrolled 19 ASA I-II patients with acute or chronic cervical lesions.52 ftey were pre- medicated and sedated with intravenous mida- zolam plus remifentanil. All patients were awake during fiberoptic intubation. Smooth intubation was considered to have failed when patients ex- hibited sustained and repetitive coughing with head lift during the procedure. Intubation time, number of attempts, adverse events, and hemo- dynamic variables were also recorded. fte EC50 of remifentanil for suppressing sustained and repetitive coughing with head lift during awake nasotracheal intubation was 2.33±0.38 ng/mL and the EC95 of remifentanil was estimated to be 3.38 ng/mL. Most patients tolerated the procedure well as reflected by the satisfaction score. All patients were cooperative throughout the procedure. fte median intubation time was longer in patients with failed smooth intubation compared to those with smooth intubation. Al- COPYRIGHT 2013 EDIZIONI MINERVA MEDICA CHIUMELLO A yEAR IN REVIEW IN MINERVA ANESTESIOLOGICA 2012 though midazolam was administered, more than half of the patients recalled the fiberoptic intu- bation procedure; higher dose of midazolam or propofol may decrease the patient’s recall, but this could results in profound sedation and hy- poventilation. Despite the recall, most patients were satisfied with the fiberoptic intubation pro- cedure. Cardiovascular anesthesia A comparison between traditional hemody- namic pressumetric measurements and volu- metric parameters derived from transthoracic echocardiography (TTE) and transpulmonary thermodilution (TPTD), was performed in thir- teen neonates and infants scheduled for correc- tive cardiac surgery.53 Significant correlation was found between TTE and TPTD (PiCCO sys- tem), particularly with regards to the global end- diastolic volume index and the fractional short- ening. In addition, the authors pointed out the importance of following the trends of volumetric parameters rather than absolute values, and the need to confirm the association of the trends be- havior with an improved outcome in the future. Platelets and coagulation were studied in twenty-two patients of four years of age or less, scheduled for cardiac operations.54 Divergent ef- fects of platelet count and function, measured with multiple electrode aggregometry TRAP- test, on postoperative bleeding was found. INR increase, aPTT prolongation, and the degree of thrombocytopenia, correlated with bleeding at multivariate analysis. Cossu AP et al. in a small prospective, ran- domized study investigated the possible adverse effects of a less-invasive surgical technique, off- pump coronary artery bypass (OPCAB) using microdialysis.55 An important message is that management of older and sicker coronary pa- tients without the support of cardiopulmonary bypass can be a “double-edged sword”, if hemo- dynamics are not adequately supported. Heart dislocation during OPCAB may induce a low- output state and an oxygen debt, which some patients are simply not able to pay during the immediate postoperative period. fte increased risk of tissue hypoperfusion demonstrated in the off-pump patients would force caregivers to check perioperative hemody- namics more carefully and to optimize oxygen delivery. Bedside microdialysis may become a useful monitor in the next future.56 Functional hemodynamic monitoring is per- formed using different devices available on the market, which use pulse contour analysis and/or transpulmonary methodology, and specific pro- prietary algorithms. fteir validation is still on- going, as well as the threshold values of the fluid responsiveness markers, that are more efficacious in predicting when fluids are not to be given rather than when extravolume can be infused. Cecconi et al. analyzed prospectively a small group of 31 surgical patients scheduled for high- risk surgery, immediately after ICU admission, using the mini-invasive PulseCO algorithm of Lidco Plus. A stroke volume optimization proto- col was followed, which allowed to discriminate 39% of fluid responders, not predicted by static parameters. Pulse pressure variation showed a better performance, the cut-off of >13% was similar to previous literature.57 Feltracco et al. in an elegant review pointed out the importance of cardiovascular monitoring during anesthesia for liver transplantation, due to the condition of hyperdynamic circulatory state and myocardial dysfunction in end-stage cirrhosis, often associated with various degrees of pulmonary hypertension.58 fte surgical tech- nique may affect the hemodynamic stability of the transplanted patient. Intraoperative optimal cardiac function and fluid balance preservation, are the more challenging objectives and require reliable hemodynamic monitoring tools. Apparently normal hemodynamic parameters and markers of tissue oxygenation can mask early derangements of capillary bed recruitment and perfusion, with subsequent cell hypoxia and death. Reliable and prompt monitoring of microcirculation may avoid or limit end-organ dysfunction and improve outcome in high-risk patients. Similarly to gastric-arterial PCO2 gap measured by gastric tonometry, rectal-arterial PCO2 gap can be considered a marker of gut hypoperfusion and damage.59 Data from recent studies showed a marked reduction of the pro- portion of perfused vessels in the rectal mucosa COPYRIGHT 2013 EDIZIONI MINERVA MEDICA A yEAR IN REVIEW IN MINERVA ANESTESIOLOGICA 2012 CHIUMELLO during the immediate postoperative course in elective on-pump cardiac surgery patients, even in the absence of altered microcirculatory blood flow indexes. Management of ventilation during cardiac surgery merits attention as pulmonary compli- cations are leading cause of postcardiac surgical morbidity, prolonged hospital stay and increased costs. Positive end-expiratory pressure (PEEP) in cardiac surgery has traditionally been underu- tilized for fear to decompensate the heart. One hundred twenty one uncomplicated coronary artery bypass graft (CABG) patients managed with two different ICU ventilatory protocols, were retrospectively evaluated for possible wean- ing differences linked to the level of PEEP cho- sen.60 fte results of the study confirmed that higher levels of PEEP did not confer sustained advantages in terms of arterial oxygenation, were associated with longer sedation with propofol and an higher cumulative fluid balance.60 Pa- tients were discharged from ICU independently of the PEEP protocol followed, and no informa- tion was given on the subsequent course of the patients. Chasing ambitious objectives or simply applying fixed protocols may prove counterpro- ductive or futile, particularly if they are applied indiscriminately and do not result in improve- ment of the postoperative outcome.61 fte review by Owczuk et al. focused on the interaction between anesthetics and a particu- lar, often neglected, aspect of EKG, namely the QT interval, corrected QT/QTc, and the related long QT syndromes (LQTS). Anesthesia care of patients with known QT prolongation has to in- clude perioperative measures aimed at decreasing the risk of malignant ventricular arrhythmias.62 fte weaning process from mechanical ventila- tion is still a challenging issue in intensive care, above all in the presence of a failing heart. fte main problem is to contextualize the heart-lung relationship in the critically ill patient, and to quantify the contribution of either one to the success or failure of the weaning trial. Echocar- diography and bio-humoral markers have been proposed as prognostic tools available in the daily practice, but alone they are unable to pre- dict the outcome of the respiratory weaning. Gerbaud et al. showed that elevated values be- fore the attempt to extubate critical patients only confirm the frailty of the heart-lung functional balance. ftey suggest to better stabilize the heart function before trying to wean the patient from the ventilator.63 Delirium and sedation Delirium is common both in ICU and on the hospital wards, often undiagnosed, multifacto- rial in origin and associated with increased mor- bidity and mortality. Colombo et al. conducted a two-cycle prospective audit to determine the prevalence of delirium and to assess the effect of a reorientation protocol, based on mnemonical and environmental stimulation, on the incidence of delirium.64 ftey identified age, and the asso- ciation of midazolam with opioid infusion as in- dependent negative predictors of delirium. fte same patient normalised this risk during phase II, due to the reorientation strategy employed. Karir et al. provided a snapshot of sedation practices in a retrospective observational study of critically ill patients mechanically ventilated for more than 14 days over a two-year period.65 Although patients were managed according to a standardized protocol for sedation and analge- sia, which included daily interruption of seda- tion and titration towards a targeted endpoint, considerably high cumulative doses of sedatives and analgesics were revealed. fte authors found the history of substance abuse to be strongly as- sociated with a greater sedative and opioid need, whereas alcohol abuse was associated with a 50% reduction of same. Less sedatives were used in older patients, with a 3% reduction in cumula- tive dose for every additional year of age. In their accompanying editorial, Richards et al.66 shared the view of Fan E, whereby ICU patients should ‘wake up, get up and get out’.67 ftey argued that analgesia and interventions such as reassurance and manipulation of environ- mental factors are paramount. Hypnotics should be used only in the setting of severe respiratory failure where muscle relaxants are required. fte expert opinion of Hilbert et al. focused on sedation during non-invasive ventilation.68 ftey revised the use of opioids, dexmedetomi- dine, and propofol to mitigate discomfort and COPYRIGHT 2013 EDIZIONI MINERVA MEDICA CHIUMELLO A yEAR IN REVIEW IN MINERVA ANESTESIOLOGICA 2012 achieve sedation to a point where patients were arousable and gas exchange improved. Pilot studies suggested that continuous infusion of a single sedative agent should be favored. Pediatric setting Amigoni et al. surveyed analgesia and sedation practices in 24 Italian Pediatric ICUs.69 ftey found that an opioid plus midazolam was used in all instances, 66.6% of units administered an ad- ditional bolus before procedures, only 50% the units used regular monitoring for analgesia and sedation, whereas only 25% monitored with- drawal regularly. In the accompaning editorial, Halley GC highlighted the challenging nature of analgesia and sedation in the pediatric setting.70 However, monitoring was essential in order to avoid oversedation and the associated morbidity. fte author advocated a multimodal approach to analgesia and sedation as part of patient-centred pathways, alongside a system of monitoring and daily evaluation of therapy to ensure this therapy remained goal orientated. Blankespoor et al. piloted a post-hoc down- ward revision of the five-point severity scale of the Pediatric Anesthesia Emergence Delirium items with the aim of designing a more objec- tive bedside-tool, useful to nurses, intensivists and psychiatrists alike.71 fte proposed ternary revision demonstrated good internal consist- ency, high inter-rater agreement, 100% sensitiv- ity, 97% specificity, and unchanged discrimina- tive accuracy at a suggested cut-off point of 8. However, future prospective work is needed to test the diagnostic accuracy of this condensed ternary rating scale. Nacoti et al. evaluated the effects of periodic sigh breaths during postoperative mechanical ventilation in 20 children who underwent ma- jor surgery.72 Each subject was ventilated with and without sigh breaths for one hour each in random sequence. After ventilation with sigh breaths, respiratory drive decreased, PaO2/FiO2 increased, and PaCO2 decreased without any change in minute ventilation. Although the size of sigh was large (average value 28.8 mL/Kg), hemodynamic parameters remained stable and no complication (pneumothorax) was observed. Pain management In the last decade increasing attention has been given to acute and chronic pain management. Pain is becoming a true social and health concern as it involves more than 49 million people in Eu- rope.73 Despite the tremendous number of arti- cles published on this topic (more than 14000 articles on pain published in 2011) 74 and the Declaration of Montreal, which recognizes ad- equate pain management as a fundamental right of every citizen,75 there are still several topics that need to be better addressed and investigated in order to reach optimal pain management. Bonezzi et al. stressed that chronic pain is not simply classifiable as “a matter of time”.76 fte authors suggested three different categories: i) patients with a chronic disease in which chronic pain is related to the underlying chronic condi- tion; ii) patients with a chronic disease in which pain is also sustained by new pathophysiological mechanisms; and iii) patients with chronic pain in whom pain is no more related to the initial in- jury but is sustained by new mechanisms. Even though this classification could help physicians better identify pain pathophysiology, additional efforts are needed to succeed in adequately con- trolling acute and chronic pain. A fascinating recent research topic is that of genetics and pain. ftere are some “chronic pain syndromes” in which a possible heritable risk exists.74, 77-79 Genetics could be involved in three different aspects:80 pain susceptibility (how patients could feel pain caused by a spe- cific noxious stimulus 81 and how patients could develop chronic pain after an acute lesion), drug metabolism (i.e. previous identification of pa- tients with impairment of cytochromes) 82 and predictability of drug response/side effects.83 In their comprehensive review Finco et al. analyzed the literature with regards to how genetics could guide a more personalized opioid therapy.84 ftey focused specifically on the extensively stud- ied genes, such as COMT, OPRM1, CyP2D6, MC1R, ABCB1, GCH1 and TRPV1. fte au- thors concluded that, despite the huge amount of data, there is no clear evidence about a specific trait that could predict pain intensity or the risk to develop chronic pain. COPYRIGHT 2013 EDIZIONI MINERVA MEDICA A yEAR IN REVIEW IN MINERVA ANESTESIOLOGICA 2012 CHIUMELLO Even though classifying and predicting acute postoperative pain is easier than for chronic pain syndromes, its management continues to be challenging.85 It is well demonstrated that optimal postoperative pain management can improve outcome ensuring early recovery, as it represents one of the mainstays of fast track sur- gery.86 Adequate postoperative analgesia could be achieved through efficient and standardized postoperative pain protocols 87 including careful use of available drugs85 and regional anesthesia techniques.88 In 2006 Tufano et al. evaluated the type of service available at 34 Italian hospitals, for the management of mild-to-moderate postoperative pain.89 ftey found that only 16.7% of hospitals had an acute pain service and less than 50% used standardized postoperative pain protocols. Of the prospectively evaluated 1952 patients, more than 15% suffered mild to severe pain. Other important information emerging from this sur- vey was the low rate of use of Patient Controlled Analgesia modalities and that 20% of patients did not receive any pain medication at all in the postoperative period. ftis survey highlighted the room for improvement in the management of postoperative pain in Italy. ftese data were successively confirmed in 200990 and 2010.91 Both hyperalgesia 92 and acute tolerance 93 in- duced by remifentanil are real concerns. ftere is clear evidence from animal data that N-methyl- D-aspartate (NMDA) receptors are involved in maintaining these phenomena.94 However, re- sults from human clinical trials are still equivo- cal.95, 96 Liu et al. in a meta-analysis, examined the evidence for the use of NMDA receptor antagonists (ketamine and magnesium sulfate) to reduce these phenomena.97 ftey considered the following outcome measures: reduction of postoperative pain, reduction of postoperative analgesics consumption, time to first analgesia and side effects of NMDA antagonists and other postoperative analgesics. ftey included 14 rand- omized clinical trials (10 used ketamine and four magnesium sulfate) with a total of 623 patients. fte use of NMDA antagonists reduced pain only in the first four postoperative hours. ftey failed to reduce analgesic consumption, pain be- yond the first hours and incidence of side effects. Hence, this meta-analysis did not support the use of NMDA antagonists for the prevention of opioid-induced hyperalgesia or tolerance. Suppa et al. conducted a clinical randomized double-blind placebo-controlled trial in patients undergoing a defined anesthetic technique (spi- nal anesthesia to prevent central sensitization) for a specific type of surgery (caesarean section). ftey hypothesized that S-ketamine (0.5 mg/ Kg after childbirth followed by 2 µg/Kg/min iv for 12 hours) was useful in reducing opioid consumption.98 Even though the sample size was small, they found an important difference (more than 30%) in opioid consumption in the first 24 hours. Nevertheless, in the S-ketamine group there were more side effects, such as di- plopia, nystagmus, dizziness, etc., even if none of them was considered bothersome by patients. ftis trial underlined the potential for ketamine to be considered part of multimodal therapy in order to take advantage of its anti-allodynic ef- fect in humans.99 Elsewhere, S(+)-ketamine (administered con- tinuously for 60 hours) was compared to place- bo, with respect not only to postoperative pain, but also chronic post-surgical pain (CPSP) at 1, 3, 6 months after thoracic surgery. Perioperative analgesia was achieved with intra- and postoper- ative epidural administration of levobupivacaine and sufentanil.100 fte authors did not demon- strate any benefit of S(+)-ketamine in reducing postoperative pain or CPSP. Of note the inci- dence of CPSP was really low in both groups. No difference in side effects between the two groups was found. fte lower incidence of CPSP in the latter trial could be explained by the opti- mal control of postoperative pain.101-103 Further- more, epidural local anesthetic administration in this study, could have overcome the possible beneficial effect of S(+)-ketamine. Froeba and Adolph dedicated their editorial to CPSP following cesarean section.104 fte eti- ology is multifactorial and the incidence may be up to 18%.104 fte severity of postoperative pain seems to correlate with the incidence of CPSP. Other authors report that pain and de- pression immediately after childbirth predict pain at two months only and persistence of pain COPYRIGHT 2013 EDIZIONI MINERVA MEDICA CHIUMELLO A yEAR IN REVIEW IN MINERVA ANESTESIOLOGICA 2012 beyond one year is very low in these patients.105 Certainly, NMDA receptors play a central role in the mechanism of chronic and pain onset. NMDA receptor activation induces central sen- sitization by long-term potentiation. fterefore the use of an antagonist such as ketamine should be the ideal drug to reduce not only postopera- tive pain and analgesic consumption but also the incidence of chronic pain. Many reports do not support this thesis and the efficacy of these drugs is questionable because many factors can be im- plicated.106 Obviously, the increasing use of regional an- esthesia techniques has also led to concerns about their possible side effects.107, 108 Even if peripheral nerve block complications are rarer than those from central blocks,109, 110 they can be severe and should always be considered, espe- cially in the more fragile. Divella et al. published a randomized con- trolled trial comparing oral controlled release oxycodone plus acetaminophen with continu- ous epidural administration of levobupivacaine and sufentanil, in patients following total hip replacement.111 fte authors evaluated pain and side effects on the first three postoperative days. ftey found that oral therapy could be more ef- fective in controlling pain at rest than epidural analgesia on the second and third postoperative day. Regarding dynamic pain, results were con- flicting: on the first postoperative day epidural treatment provided better pain control but oxy- codone was more effective on the third postoper- ative day. fte authors concluded that oral treat- ment could be a valid alternative in all patients in whom regional anesthesia techniques failed or were contraindicated, such as in those on new anticoagulant drugs.112 Transcutaneous electrical nerve stimulation (TENS) has been reported useful in reducing postoperative morphine consumption and asso- ciated side effects.113, 114 Lan et al. investigated, in a randomized clinical trial in elderly patients (over 65 years) undergoing hip arthroplasty, TENS on six acupoints (on the arms and on the legs).115 TENS reduced fentanyl requirement by more than 20% on the first and the second post- operative day. ftese data are even more impor- tant as they were drawn from elderly patients, a fragile population in whom sometimes regional anesthetic techniques are not feasible and in whom the relationship between opioid request and clinical side effects is even stronger.116 Finally, spinal cord stimulation (SCS) is indi- cated in ‘failed back surgery syndrome’ patients with predominant radicular-neuropathic leg pain,117 even if there are some good data avail- able for the treatment of axial pain.118 Despite existing evidence for the effectiveness of SCS and specific guidelines for treatment of neuropathic pain,119 its mechanism of action in controlling peripheral neuropathic pain is still debated.120 Buonocore et al. conducted an observational study on 10 consecutive patients with SCS for lower limb chronic pain, to elu- cidate the mechanism of action of SCS121 ftey demonstrated that SCS has an inhibitory effect on somatosensory evoked potentials (SEPs), confirming data published in another study.122 ftis inhibitory effect was rapidly reversible when SCS was switched off. Hence the authors demonstrated that SCS acts by inhibiting SEPs, independently from basal conditions, support- ing the interesting hypothesis that SCS could act through a “collision” of action potentials trav- elling in opposite directions. However, further studies are still needed to elucidate the mecha- nism of action of SCS, including the specific correlation between inhibition of SEPs and pain relief obtained.121 Zanatta et al. investigated if a painful electrical stimulation could be validated as a provocative test predictor of patient’s outcome, in patients with post anoxic coma in the acute phase.123 In- deed, it is known that the presence of middle- latency cortical somatosensory evoked potentials is associated with favorable prognosis in patients with post anoxic coma.124, 125 Sedation Sedation and analgesia are commonly used in critically ill patients in order to optimize pa- tients’ comfort. However they can present sev- eral side effects. McGrane et al. discussed the relevant pharmacology of commonly prescribed analgesics and sedatives as well as an evidence based approach of best sedation practices in COPYRIGHT 2013 EDIZIONI MINERVA MEDICA A yEAR IN REVIEW IN MINERVA ANESTESIOLOGICA 2012 CHIUMELLO critically ill patients.126 Problems associated with oversedation are: prolonged mechanical venti- lation, muscle atrophy, nosocomial infections and development of withdrawal syndrome.127, 128 Continuous assessment of sedation is recom- mended in critically ill patients. Amigoni et al. evaluated sedation in a pediatric intensive care unit using the comfort behavioural scale (CBS) and the bispectral index (BIS) in terms of pa- tient’s outcome.129 fte level of agreement be- tween the CBS and BIS was weak. fte length of stay and duration of sedative administration were significantly shorter in adequately sedated patients. In an editorial, Vazquez Martinez J sug- gested that, in the absence of a gold standard for evaluating the level of sedation in the critically ill child, the electroencephalogram, clinical and hemodynamic parameters are complementary tools for optimizing sedation in pediatric inten- sive care units.130 Most guidelines for sedation in intensive care suggest a combination of hypnotics and opiates. Among opiates, remifentanil is often chosen based on its short context sensitive half-life inde- pendent of renal or hepatic metabolism. Futier et al. assessed the impact of substituting remifen- tanil for sufentanil in an analgesia based seda- tion protocol on sedation goal achievement.131 Remifentanil was associated with significantly shorter mechanical ventilation time and inten- sive care stay. fte sedation target was reached more often with remifentanil with lower use of hypnotic agents. In addition, remifentanil may represent an alternative to other analgesic and sedative drugs.132 Inadequate sleep in critically ill patients is as- sociated with deterioration in mental status, de- crease in pain threshold, metabolic dysfunction and alteration of circadian rhythm.133, 134 Little et al. in an observational study investigated in- tensive care practices which contributed to sleep deprivation.135 fte most frequently cited reasons for poor quality sleep were noise, pain, light, loud talking and the presence of intravenous catheters. In addition, patients who received in- travenous sedatives reported better quality sleep. Simple measures such as decreasing staff con- versation, quietness and the nocturnal lighting might improve sleep quality. Ethics and comunication As a result of informed decision, patients can accept or refuse any medical procedure. fte in- formed consent is the basis of a professional re- lationship between patient and physicians both from a legal and ethical point of view. Giampieri M summarized the key points for a rational ap- proach to the informed consent process in elder- ly persons.136 Along the same lines, Abd-Elsayed et al., tested the hypothesis that presentation of consent documents in an enhanced format would improve the patient’s attention, under- standing and willingness to consent to clinical research.137 ftree informed consents to partici- pation in randomized trials were presented in a standard and an enhanced format (i.e. printed on 20 pound, cream colored band paper and presented in a blue folio). fte enhanced format did not improve the rate of consent to partici- pate in clinical trials. Family members can be very helpful to pa- tients in intensive care units. However, when a family members is a health care worker, this can complicate the medical care of their hospitalized relative.138, 139 Bramstedt et al. presented a clini- cal series on this unusual topic offering possible suggestions in order to set boundaries with clini- cian relatives.140 In the accompanying editorial, Giannini A suggested that “light touch” may be the most effective expression of the attention and respect of a physician involved in the care of his parent.141 References 1. Schwartz AE. Computer processed EEG and the explora- tion of the twilight zone. Minerva Anestesiol 2012;78:631- 32. 2. young WL, Moberg RS, Ornstein E, Matteo RS, Pedley TA, Correll JW et al. Electroencephalographic monitoring for ischemia during carotid endarterectomy: visual versus computer analysis. J Clin Monit 1988;4:78-85. 3. Pilge S, Kreuzer M, Kochs EF, Zanner R, Paprotny S, Sch- neider G. 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Minerva Aneste- siol 2012;78:291-6. 40. Laituri CA, Garey CL, Pieters BJ, Mestad P, Weissend EE, St Peter SD. Overnight observation in former premature infants undergoing inguinal hernia repair. J Pediatr Surg 2012;47:217-20. 41. Lopez T, Sanchez FJ, Garzon JC, Muriel C. Spinal anesthe- sia in pediatric patients. Minerva Anestesiol 2012;78:78- 87. 42. Hwang JW, Oh Ay, Song IA, Na HS, Ryu JH, Park HP et al. Influence of a prolonged lateral position on induction of spinal anesthesia for cesarean delivery: a randomized con- trolled trial. Minerva Anestesiol 2012;78:646-52. 43. Scheiermann PandBreitkreutz R. Spinal anesthesia and prolonged lateral position for cesarean delivery: isn’t that dangerous? Minerva Anestesiol 2012;78:633-5. 44. Borghi B, Tognu A, White PF, Paolini S, Van Oven H, Au- rini L et al. Soft tissue depression at the iliac crest promi- nence: a new landmark for identifying the L4-L5 inter- space. Minerva Anestesiol 2012;78:1348-56. 45. 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Falcetta S, Pecora L, Orsetti G, Gentili P, Rossi A, Gab- banelli V et al. fte Bonfils fiberscope: a clinical evaluation of its learning curve and efficacy in difficult airway manage- ment. Minerva Anestesiol 2012;78:176-84. 49. Merli G. Airway management and tracheal intubation: where can we improve? Minerva Anestesiol 2012;78:144-6. 50. Ilies C, Fudickar A, ftee C, Dutschke P, Hanss R, Doerges V et al. Airway management in pediatric patients using the Glidescope Cobalt(R): a feasibility study. Minerva Aneste- siol 2012;78:1019-25. 51. fteiler L, Fischer H, Voelke N, Basciani R, Hasty F, Greif R. Survey on controversies in airway management among anesthesiologists in the UK, Austria and Switzerland. Mi- nerva Anestesiol 2012;78:1088-94. 52. 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Anestesia e Rianimazione Dipartimento di Anestesia, Rianimazione (Intensiva e Subintensiva) e Terapia del Dolore Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italia. E-mail: davide.chiumello@minervamedica.it