Gao P. Liu

Evaluating effective dose of dexmedetomidine: onset time of drug is critical.

Sir, We read with interest the article by Kwak et al evaluating effective dose of dexmedetomidine for laryngeal mask airway insertion with propofol 2.0 mg/kg. In this study, the authors have correctly used a Dixon’s up-and-down method to obtain the median effective dose (ED50) of dexmedetomidine and openly discussed the limitations of their work. However, in our view, some defects in the design of this study may have made interpretation of their conclusions questionable. In the operating room, each patient received a predetermined single dose of dexmedetomidine over 2 min. One minute later, anaesthesia was induced with propofol 2.0 mg/kg. Sixty seconds after completion of propofol administration, the laryngeal mask airway was inserted. That is, laryngeal mask airway insertion is commenced about 2.5 min after dexmedetomidine administration and 1 min after propofol administration. It must be emphasised that the use of dexmedetomidine as a general anaesthetic is limited by speed of onset and dose-related haemodynamic sequelaes such as hypotension and bradycardia. Because onset of dexmedetomidine is slower than some sedative and analgesic agents (such as propofol, ketamine, and remifentanil), it requires planning to optimise its use for maximal effect. After intravenous administration in healthy adult volunteers, dexmedetomidine has an onset of action after approximately 15 min. To achieve adequate clinical efficacy and minimise cardiovascular side effects, it is recommended that when used as an adjunct to general anaesthesia, a singledose dexmedetomidine should be given 15 min before anaesthesia induction. In previous studies evaluating clinical pharmacology of dexmedetomidine, anaesthesia induction is also performed at least 15 min after dexmedetomidine administration. Moreover, after a bolus injection of propofol 2.0 mg/kg, the times required to reach peak effect is about 100–120 s. Thus, we argue that when anaesthesia is induced with dexmedetomidine and propofol, clinicians should deliver the two drugs in such a way that their peak effects occur at the same time and hence obtain most effective sedation and analgesia for subsequent airway procedure. We believe that if this drug administration method was applied in the study design, a different median ED50 of dexmedetomidine for laryngeal mask airway insertion would have been obtained. Conflicts of interest: There are no potential conflicts of interest for this work. Funding: No authors received financial support.

Assessing biomarker of acute kidney injury and its association with worse outcomes after cardiac surgery

Stephan Segerer, Yuya Sugano, Maja T. Lindenmeyer, Ines Auberger, Urs Ziegler, Clemens D. Cohen, Stephan C.F. Neuhauss and Johannes Loffing Institute of Physiology, University Hospital, Zurich, Switzerland; Division of Nephrology, University Hospital, Zurich, Switzerland; Zurich Center for Integrative Human Physiology, Zurich, Switzerland; Institute of Anatomy, University of Zurich, Zurich, Switzerland; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland; Center for Microscopy and Image Analysis, University of Zurich, Zurich, Switzerland; and Division of Nephrology, Klinikum Harlaching, Munich, Germany Correspondence: J. Loffing, Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. E-mail: johannes.loffing@anatom.uzh.ch

Comparing Local Infiltration and Continuous Femoral Nerve Block for Pain Relief After Total Knee Arthroplasty

The recent article by Kurosaka et al [1] comparing efficacy of local infiltration analgesia and continuous femoral nerve block for pain relief after total knee arthroplasty (TKA) was of great interest. They showed that local infiltration was associated with an improved early postoperative pain relief during initial 24 hours after surgery. Many things of this study were well done. The authors used a prospective, 2-arm, parallel-group, randomized, controlled design. They chose a well-validated end point of postoperative pain assessment: visual analog scale (VAS) score. They had attempted to control most of known factors affecting postoperative pain after TKA, such as age, gender, body mass index, preoperative pain intensity, type of surgery, and so forth. Furthermore, they openly discussed the limitations of their work. All these are strengths in the study design. We can learn from their example but would like to ask some questions about their methodology. First, mean age of patients was>75 years, andmean VAS score of preoperative pain was >55 points. Chronic pain often causes psychological disorders. It has been shown that preoperative psychological comorbidities, such as anxiety, depression, negative mood, and pain catastrophizing, are highly prevalent in patients undergoing TKA, especially for elderly patients [2,3]. Furthermore, preoperative psychological comorbidities have been significantly associated with acute postoperative pain after TKA [3,4]. In addition, preoperative uses of anticonvulsants, antidepressants, and opioids have been shown as significant predictors for moderate to severe acute postoperative pain after TKA [5]. It was unclear whether the 2 groupswere comparablewith respect to preoperative psychological comorbidities and long-termdrug use of patients.We are concerned that imbalance in these preoperative factors between groups would have confused interpretation of their results. Second, all surgeries were performed under general anesthesia, but the readers were not provided with detail of anesthesia. We were very interested in knowing whether dose of opioid and analgesic drugs used during perianesthetic period was comparable between groups. When early postoperative pain between groups is compared, standardization of perianesthetic use of opioid and analgesic drugs should be a crucial component of study design. It has been shown that intramuscular injection of morphine before

Rationale for a modified endotracheal tube for intubation using video laryngoscopy

To the Editor, We were greatly interested in the recent article by Emsley and Hung that described endotracheal tube (ETT) modifications for intubation using video laryngoscopy (VL). However, we believe that there are several aspects of this article that need clarification. First, the authors reported that they successfully performed intubation in more than ten patients using a styletted, straight, Fastrach wire-reinforced silicone tube (Teleflex Medical, Markham, ON, Canada) with a C-MAC video laryngoscope (Karl Storz, Tuttlingen, Germany) without the ETT getting ‘‘hung up’’ on the anterior tracheal wall. We believe, however, that the problem of ETT being ‘‘hung up’’ on the anterior tracheal wall occurs more often during intubation using the more angulated VLs, such as GlideScope (Verathon Medical, Bothell, WA, USA) and McGrath (Aircraft Medical, Edinburgh, Scotland) VLs. Compared with the angle of the blade at the base of the tongue characteristic of these VLs, the trachea descends from the larynx into the thorax at a posterior angle. The difference between these angles creates the potential problem of the ETT being ‘‘hung up’’ on the anterior tracheal wall. The more angulated VLs require use of a stylet, whereas the more conventional, Macintosh-type blade of the C-MAC VL allows successful intubation without using a stylet. Accordingly, as no stylet or preshaping of the ETT is required in most of these cases, difficulty passing the ETT because of impingement on the anterior tracheal wall does not occur as often with the CMAC VL. Thus, the authors’ use of the C-MAC VL to validate the hypothesis whether a pre-curved styletted ETT can avoid the ETT from being ‘‘hung up’’ during intubation with VL may be misleading. Second, to show the degree to which the standard ETT with an anterior angulation curves upward as a stylet is withdrawn, the authors used a malleable stylet to pre-form the distal part of the ETT into a 90 ‘‘hockey stick’’ shape. In our experience, the greater the distal angle of the precurved styletted ETT, the more the distal part of the ETT curls upward during withdrawal of the stylet. When intubation is performed with the various angulated VLs in clinical practice, it is generally recommended that the ETT be pre-shaped with a malleable stylet to an angle similar to the blade curvature, such as an angle of 60 for GlideScope VL. Thus, their exaggerated distal ETT angle of 90 may limit the clinical significance of their results. Finally, the modifications they suggested for incorporation into a special VL ETT might already be present in a commercially available, specially designed ETT for the GlideScope VL, such as the Parker FlexTip ETT (Parker Medical, Highlands Ranch, CO, USA). This ETT has a standard anterior curvature and a symmetrical tip with a ski-tip shape. When combined with the GlideRite rigid stylet (Verathon Medical, Bothell, WA, USA), this ETT (compared with the standard ETT) can significantly improve intubation with the GlideScope VL. This letter is accompanied by a reply. Please see Can J Anesth 2016; 63: this issue.

Assessing the protective effect of remote ischemic preconditioning on acute kidney injury after coronary artery bypass graft surgery.

To the Editor: In a recent article of Gallagher et al.1 assessing the effect of remote ischemic preconditioning on the incidence of acute kidney injury (AKI) after coronary artery bypass grafting surgery, perioperative hemoglobin levels and managements were not included in data analysis. Actually, preoperative anemia is common among patients undergoing coronary artery bypass grafting surgery and is associated with independently increased risks of postoperative adverse myocardial and renal events.2 Furthermore, hemodilution anemia during cardiopulmonary bypass has been associated with an increased incidence of postoperative AKI. Especially, the combination of intraoperative hemodilution anemia and hypotension can synergistically act to increase the risk of AKI after cardiac surgery.3 Similarly, intraoperative systolic blood pressure decrease relative to baseline has also been independently associated with AKI after coronary artery bypass grafting surgery.4 We are concerned that any imbalance in these factors would have confounded interpretation of their results. Finally, serum neutrophil gelatinase-associated lipocalin (NGAL) is known as a troponin-like biomarker for AKI. We noted that median serum NGAL levels at 24 h after surgery in the two groups were about two times the baseline values. Furthermore, measured serum NGAL levels at every observed time point had highly variable ranges. However, we were not provided with the cutoff value of serum NGAL for diagnosis of AKI and the number of patients in each group who had a higher NGAL level than the cutoff value.

Association of Preoperative Anemia With Complications and Mortality Following Total Joint Arthroplasty.

We read with interest the recent article by Viola and colleagues [1] assessing association of preoperative anemiawith complications andmortality following total joint arthroplasty (TJA). The power of this single institution study is its use of a prospective database that includes a large cohort of patient undergoing TJA and most of known factors affecting postoperative complications and mortality of such surgical patients. Furthermore, the authors usedmultivariate analysis to determine the effects of preoperative anemia on study outcomes. In our view, however, several issues that werenotwell addressed in this retrospective analysismight havemade interpretation of their results questionable. First, the preoperative hemoglobin levels were determined at a maximum of 28 days and a minimum of 45 minutes preoperatively. This may not be a real representation of hemoglobin levels on surgery day in some patients, especially for patients who are preoperatively identified as anemic while on the waiting list. In the anemic patients, correcting treatments of preoperative preparation have been shown to change the preoperative hemoglobin levels and postoperative outcomes. In a prospective study of 322 patients undergoing TJA, the anemic patients were preoperatively provided oral iron therapy while on the waiting list (n = 26). The transfusion rate was 3% in the nonanemic group versus 23% in the anemic group treated with oral iron (P b 0.05). Of anemic patients treated with oral iron, the transfusion rate was 9% in those who responded to iron therapy and increased their preoperative hemoglobin levels more than 12 g/dl (n = 11) versus 33% in those who did not (P b 0.05). The mean length of hospital stay was significantly longer in anemic nonresponders than in anemic responders and nonanemic patients (P b 0.05) [2]. Furthermore, a recent pooled analysis of observational data from2547patients undergoingmajor orthopedic surgery even showed that very-short-term perioperative intravenous iron therapy with or without erythropoietin was associated with reduced transfusion rate and shortened length of hospital stay [3]. Second, Viola and colleagues did not clearly describe whether the mortality reported in this study was hospital mortality, 30-day mortality or longer-termmortality. A single-center analysis of 1998 patients undergoing TJA shows that there are significant differences in mortality risk-factors between early and late periods after surgery. The early mortality is most likely related to the surgery and perioperative managements, and lasts about a month. However, the longer-term mortality primarily represents the natural process of aging or potential diseases [4]. Third, Viola and colleagues did not provide the statistical results of comparing demographic data between normal and anemic patients. According to the data provided in their Table 1, by statistical calculations using the EpiCalc 2000 statistic software, we noted that gender, age, body mass index, Charlson comorbidity score and types of surgery were significantly different between normal and anemic patients. Without adjusting for these data, a direct comparison of crude mortality between two groups using a Chi-square may produce an uncorrected conclusion. Regarding effect of preoperative anemia on postoperativemortality, we argue that the conclusion should bemadebased on the adjusted odds ratio. Furthermore, degree of preoperative anemia has been associated independently with the risks of complications and mortality after major noncardiac surgery [5]. We believe that this study would have presented more persuasive results if patients were stratified by degree of preoperative anemia. Fourth, in this study, we noted that anemic patients had a higher Charlson score and a higher rate of transfusion. That is, preoperative anemia may only be a surrogate for other risk factors of postoperative complications and mortality, such as renal dysfunction, congestive heart failure, myocardial infarction, malnutrition, etc [6]. When anemia is present concomitantly with a known preoperative risk factor, it can result in a significant increase in the effect of this risk factor on postoperative outcomes [5]. Moreover, preoperative anemia is the most important predictor of perioperative transfusion, which is independently associated with complications and mortality following TJA [7]. In the presence of other risk factors, the patients tolerance for anemia is also further decreased significantly [8]. All these can give us the dilemma of differentiating these important inter-related risk factors and their relative influence on postoperative outcomes. A “kitchen sink” approach of adjusting for all available variables with multivariable analysis may lead to over-adjustment and therefore bias the true effects of preoperative anemia on postoperative outcomes. Most importantly, a retrospective study dealing with chronic exposures should distinguish between confounding and mediating variables. Perhaps, propensity-matching patients with and without preoperative anemia on the prior-defined confounders is a desirable approach to obtain total effect of anemia on postoperative outcomes via all possible pathways [9]. By using propensitymatching on potentially confounding variables and adjusting for suspected mediating variables, a retrospective study including 574,860 noncardiac surgical patients showed that preoperative anemia was associated with baseline diseases that significantly increased 30-day postoperative mortality, whereas preoperative anemia per se was a rather weak independent predictor of mortality [9]. Moreover, a retrospective study of patients undergoing TJA showed that existing comorbidities, rather than preoperative anemia, were independently associated with postoperative major complications and mortality [10]. Therefore, further studies assessing the true effects of preoperative anemia on outcomes following the TJA are still needed. Finally, their Table 2 showed a mortality of 8% in normal patients. Evidently, it is a typing mistake. The real mortality of normal patients in this study is 0.08%. The Journal of Arthroplasty 30 (2015) 2043–2044

Does the method of anesthesia really affect outcomes and survival after total joint replacement

To the Editor, We were greatly interested in the recent article by Chen et al. assessing the effects of anesthesia methods on patient outcomes and long-term survival after total joint replacement (TJR). The authors showed that, compared with patients given general anesthesia, patients given neuraxial anesthesia had better long-term survival (58.2% vs 57.3%, respectively; P = 0.009), shorter length of hospital stay (8 [7-10] days vs 8 [6-10] days, respectively; P = 0.024) and lower hospital treatment costs (

Assessing acute kidney injury in bariatric surgery patients admitted to the intensive care unit.

4,079 [3,805-4,444] vs

Use of a 90‐degree anticlockwise tube rotation to facilitate nasotracheal tube passage over the fiberscope into the trachea in pediatric patients

4,113 [3,812-4,568], respectively; P\ 0.001). The strength of this retrospective nationwide population-based study is the use of Taiwan’s National Health Insurance Database which includes both large numbers of patients undergoing TJR and many known factors affecting the postoperative outcomes of such surgical patients. Propensity-scorematching was used to reduce possible effects of confounders on study endpoints. Nevertheless, one shortcoming of propensity-score-matching is that patients who cannot be matched are excluded from analysis. The excluded patients tend to be both the sickest and the healthiest patients, leaving only the patients with moderate morbidities for group comparison. This would limit generalizability of the results. For example, before propensity-score-matching in this study, patients given general anesthesia had a higher Charlson comorbidity index score, more congestive heart failure, and mild liver disease, whereas patients given neuraxial anesthesia were notably older and had more myocardial infarction and chronic obstructive pulmonary disease. To generate two propensity-score-matched subgroups, 4.8% of patients given general anesthesia and 42.9% of patients given neuraxial anesthesia were excluded. Furthermore, the National Health Insurance Database used in this study does not include data that can potentially influence postoperative outcomes and survival, including the patients’ American Society of Anesthesiologists physical status classification, preoperative hemoglobin levels, perioperative cardiac medications, preoperative functional status, and surgical complications. This can further decrease the accuracy and inferences of propensity-scorematched subgroups adjusted for potential confounders. In this retrospective study, we were not provided with the details of anesthesia and perioperative management. Consequently, it is difficult to estimate the extent of influence that anesthesiologists’ interventions might have on postoperative outcomes and long-term survival. Actually, in clinical practice, anesthesiologists would have selected anesthetic methods based on patients’ baseline characteristics and pre-existing mobidities. Furthermore, intraoperative blood loss, transfusion, and hemodynamic instability have also been independently associated with postoperative outcomes and mortality of patients with noncardiac surgery. In addition, a singlecentre analysis of 1,998 patients undergoing TJR shows that there are significant differences in mortality risk factors between early and late periods after surgery. Early mortality, which lasts about one month, is most likely related to the surgical procedure and perioperative management; however, longer-term mortality primarily The authors of the article: Can J Anesth 2015; DOI: 10.1007/s12630015-0316-0, respectfully declined an invitation to submit a reply to the above letter.

Influences of preoperative opioid use on acute pain and analgesic requirement after total knee arthroplasty

To the Editor, With great interest, we read the recent article by Morgan and Ho [1] assessing incidence and risk factors for acute kidney injury (AKI) after bariatric surgery in an observational, multicenter study with 590 patients admitted to the intensive care unit (ICU). They found that the incidence of postoperative AKI was 17.5%. Furthermore, the multivariate analysis showed that male sex, premorbid hypertension, higher Acute Physiology and Chronic Health Evaluation II scores at admission, and blood transfusions were associated with postoperative AKI. Strengths of this study are its use of a large sample of patients from 8 specialist-run ICU admissions databases. Most importantly, the authors used appropriate statistical methods to identify the risk factors of postoperative AKI. We congratulate the authors for conducting this clinically useful research, but we would like to ask several questions about their methodology. First, AKI was determined by a comparison between baseline and peak postoperative serum creatinine (sCr) concentrations, using the modified Acute Kidney Injury Network (AKIN) criteria. However, the authors did not provide the observational duration of postoperative sCr. It must be emphasized that the AKIN criteria need to use a 48hour time window [2]. Furthermore, we would like to know whether postoperative sCr levels used for diagnosis of AKI had been corrected for fluid balance. It has been shown that dilution of sCr by fluid accumulation in critically ill patients admitted to the ICU may lead to underestimation of the severity of AKI; therefore, correction of sCr for fluid balance can improve recognition and staging of AKI [3]. In addition, the AKIN urinary output criteria were not used in this study due to the inconsistency in reliable recording across smaller participating ICUs during the study period. Wlodzimirow et al. [4] demonstrated that only use of the sCr criteria without the urine output criteria can significantly underscore the incidence and grade of AKI and significantly delay the diagnosis of AKI in adult critically ill