Xin-Long Cui

Preoperative Hemoglobin Level as a Predictor of Mortality After Aortic Valve Replacement

OBJECTIVES The predictive value of preoperative hemoglobin (HB) level on the outcome of patients undergoing valve surgery is not well established. This study evaluated the predictive value of preoperative HB level on survival after aortic valve replacement (AVR). DESIGN This was a retrospective analysis of prospectively collected data. SETTING A single-center study performed in an educational hospital. PARTICIPANTS All consecutive patients (n = 1,808) who underwent AVR between January 1998 and December 2010. INTERVENTIONS AVR MEASUREMENTS AND MAIN RESULTS Patients were classified into 4 groups according to the preoperative HB level: very low (HB of <12 g/dL in men and <11 g/dL in women), low (HB of 12-13 g/dL in men and 11-12 g/dL in women), normal (HB of 13-14.5 g/dL in men and 12-13.5 g/dL in women), and high normal (HB of ≥14.5 g/dL in men and ≥13.5 g/dL in women). The mean follow-up duration was 5.58±3.5 years, and the median follow-up duration was 5.38 years. The mean preoperative HB was 14±1.6 g/dL for men and 13.0±2.1 g/dL for women. Early mortality (≤30 days) was 6.1% in the very-low-HB group, 5.4% in the low-HB group, 3.2% in the normal HB group, and 2.3% in the high-normal-HB group (p = 0.37). Late mortality (>30 days) was 26.1% in the very-low-HB group, 23.7% in the low-HB group, 17.1% in the normal-HB group, and 12.6% in the high-normal-HB group (p<0.0001). The multivariate logistic regression model did not identify low HB as an independent predictor for early mortality. Cox regression multivariate analysis revealed both HB level, as a continuous variable, (p = 0.006), and very-low-HB level (p<0.0001), as independent predictors of late mortality. Cox regression analyses, corrected for confounders, demonstrated that low-HB level is an independent predictor for higher overall mortality (hazard ratio = 2.00, CI 1.41-2.85, p≤0.0001). CONCLUSIONS In patients undergoing AVR, preoperative low-HB level is an independent risk factor for late mortality, but not for early mortality.

Combined morphine and limb remote ischemic perconditioning provides an enhanced protection against myocardial ischemia/reperfusion injury by antiapoptosis

BACKGROUND Both morphine and limb remote ischemic perconditioning (RIPer) can protect against myocardial ischemia/reperfusion injury (IRI). This experiment was designed to assess whether combined morphine and limb RIPer could provide and enhanced protection against myocardial IRI in an in vivo rat model. METHODS One hundred male Sprague-Dawley rats were randomly allocated to six groups: sham, ischemia/reperfusion (IR), ischemic preconditioning, RIPer, morphine (M), and combined morphine and remote ischemic perconditioning (M + RIPer). Ventricular arrhythmias that occurred during ischemia and early reperfusion were scored, and serum creatine kinase isoenzyme and cardiac troponin I levels were assayed. The infarct size was determined by Evans blue and triphenyl tetrazolium chloride staining. The apoptosis in the myocardial ischemic core, ischemic border, and nonischemic areas was assessed through real-time polymerase chain reaction for Bax and Bcl-2 and with the transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay. RESULTS The infarct size, serum cardiac troponin I level, incidence, and score of the arrhythmias during the initial reperfusion were significantly reduced in the M + RIPer group compared with the IR group but did not differ significantly between the ischemic preconditioning and M + RIPer groups. Transferase-mediated deoxyuridine triphosphate-biotin nick end labeling-positive cells were significantly decreased, and the Bcl-2/Bax ratio was significantly increased in the M + RIPer group compared with the IR group. CONCLUSIONS This experiment demonstrates that combined morphine and limb RIPer provides an enhanced protection against myocardial IRI by the Bcl-2-linked apoptotic signaling pathway.

Comparative performance of GlideScope video laryngoscope and Macintosh laryngoscope in children with immobilized cervical spine.

In a crossover randomized clinical study comparing performance of the GlideScope video laryngoscope (GVL) and Macintosh laryngoscope in children with immobilized cervical spine, Vlatten et al showed that using the GVL resulted in a significantly declined glottic view. In our view, however, there are several aspects of this study that need to be clarified. First, the authors did not describe the types of the GVL used in this study. As yet, there are totally 3 types of GVL available: the conventional GVL, the Cobalt GVL and the Ranger GVL. Also, every device has 2 to 3 reusable or disposable blades available for pediatric patients. The shapes, lengths, and angulations of the blades vary among the 3 GVL devices and between the reusable and disposable GVL blades (http://verathon.com/language/en-us/ products/glidescope.aspx). For example, the disposable blades of the Cobalt GVL are narrower and longer than the reusable blades of the original GVL. This enables manipulation of laryngeal structures, while at the same time allowing more room in the oral cavity to insert the tracheal tube. Thus, addressing this issue would further clarify the transparency of this study. Second, in methods, there was no mention as to what measures, if any, were taken by the intubator to improve the laryngeal view with the GVL. Actually, the GVL camera’s field of view does not cover the tangent of the distal half of the blades, resulting in a blind area below the blade tip. For example, the blind area of the camera below the blade tip is 2 and 13 mm in small and medium reusable GVL blades available for pediatric patients, respectively. Although a small blind area below the blade tip may not interfere with laryngoscopy with the GVL, the midsize GVL blade with 13-mm width blind spot may require a more anterior direction of the camera view and optimum external laryngeal manipulation (OELM) to obtain a better exposure of the glottis. In the recent studies comparing performance of the GVL with direct laryngoscope in pediatric patients with normal and difficult airways, OELM has been shown to provide improved laryngoscopic view with pediatric GVL. We are concerned that lack of requirements for the OELM in this study may have underestimated performance of the GVL for laryngeal exposure. This perhaps is one of reasons that the GVL compared with Macintosh laryngoscope provides a worse glottic view in children. Third, in discussion, the authors stated that the participants of this study were familiar with the GVL and used it only in expected difficult airway situations. However, they did not provide the actual or least number of tracheal intubations with the GVL by each participant in pediatric patients with normal and difficult airways. In a previous study comparing performance of different video laryngoscopes (including GVL) in morbidly obese patients, the experienced intubators were required to have a minimum of 50 uses of each video laryngoscope before the study. More importantly, they did not explain whether all participants had achieved proficiency for tracheal intubation with the GVL, especially for children with a difficult airway. In this respect, we would like to repeat the opinion espoused by Behringer et al that, for the results of a comparative study to be valid, participants must be equally proficient with each airway device to avoid bias. Finally, the pictures of figures 2 and 3 in their article seem incorrect. In our opinion, the picture of figure 2 should be the laryngoscopy with the GVL in a child with increased neck extension and anterior larynx, whereas the picture of figure 3 depicts the laryngoscopy with the GVL in a child with restricted neck movement. Thus, the pictures of figures 2 and 3 should be interchanged.

Is preoperative atrial fibrillation an independent predictor of worse outcomes after coronary artery bypass graft surgery

In a retrospective study including 21,534 patients who underwent coronary artery bypass graft (CABG) surgery, Saxena et al. [1] showed that preoperative atrial fibrillation was an independent predictor of early and late mortality. Strengths of this study are its use of a large dataset from the Australasian Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database Program containing most known risk factors that can affect postoperative mortality of such surgical patients. Furthermore, the authors used univariate and multivariate logistic regression analyses to identify the predictors of early and late mortality after CABG surgery, and openly discussed some limitations of their work. However, in our view, several important issues of this study were not well addressed. First, perioperative anemia and transfusion were not included in the data analysis. Actually, preoperative anemia is common among patients undergoing CABG surgery and can increase the postoperative 30-day mortality risk by 3.4-fold [2]. In the patients undergoing CABG surgery, the lowest hemoglobin level during cardiopulmonary bypass has been associated independently with postoperative low-output syndrome, renal failure, and mortality [3]. Similarly, postoperative anemia is also common with an incidence of 44% and frequently persists for months after CABG surgery. Sustained postoperative anemia is associated with increased risks of adverse cardiovascular events and mortality. When postoperative hemoglobin level is considered as a continuous variable, every 1 mg/dl decrease in hemoglobin level is associated with a 13% increase in postoperative adverse cardiovascular events and a 22% increase in all-cause mortality [4]. We are concerned that any imbalance in the above factors among patients with and without preoperative atrial fibrillation would have confounded the interpretation of the results. Second, health status, burdens of surgery, and comorbidities are mostly important determinants of early mortality, and the

Performance of videolaryngoscope and flexible fibreoptic endoscope in simulating difficult airways.

In a manikin study, Jepsen et al. showed that anaesthesia residents performed tracheal intubation significantly faster with the McGrath videolaryngoscope (VLS) than with the flexible fibreoptic endoscope (FFE) and achieved a higher success rate in two out of three simulated difficult airway scenarios. Their results suggest potential benefits of using a VLS in difficult airway management, but there are several aspects of this study that need to be discussed.

Comparing Cardioprotective Effects of Anesthesia Methods in Patients Undergoing Elective Abdominal Aortic Surgery

To the Editor: The recent article by Lindholm et al.1 comparing cardioprotective effects of sevoflurane-based anesthesia and propofol-based total intravenous anesthesia in elective abdominal aortic surgery patients was of great interest. Many things of this study were done correctly. The authors used a prospective, randomized, open, parallel-group design and chose a sensitive and well-validated endpoint of myocardial injury: troponin release. They had a large number of subjects (193) and a consistent operation (elective major vascular surgery). Also, they had tried to control most of the known factors that could affect perioperative myocardial injury, such as age, body mass index, American Society of Anesthesiologists physical status classification, preoperative comorbidities and medications, aorta cross-clamp time, hemodynamic changes during surgery, intraoperative blood loss and transfusion, and many others. All these are strengths in the study design. However, to differentiate the effects of one factor on study endpoints, all the other factors have to be standardized in a randomized, controlled trial. In our views, several issues of this study were not well addressed. First, we would like to know why perioperative hemoglobin levels were not included in data analysis. Actually, preoperative anemia is common among patients undergoing major vascular surgery, and the presence and severity of preoperative anemia have been shown to be independent predictors of perioperative and long-term cardiac adverse events in vascular surgery patients.2,3 In addition, in a retrospective study of vascular surgery patients, Valentijn et al.4 even show that preoperative hemoglobin levels, postoperative hemoglobin levels, and intraoperative hemoglobin decreases are all related to an increased risk of 30-day postoperative cardiovascular adverse events, especially for postoperative hemoglobin levels. Second, the authors did not provide anesthetic dosage (minimum alveolar concentration [MAC]) of sevoflurane used during the surgery. It has been reported that only when concentrations of sevoflurane are 1 MAC or more, pharmacological preconditioning by sevoflurane can produce a significant protection against myocardial ischemia–reperfusion injury in the rat heart in vivo.5 Thus, it was possible that sevoflurane-based anesthesia compared with propofol-based anesthesia did not produce more cardioprotective effects because sevoflurane was given at a low dosage. Furthermore, data on the total dosages of fentanyl and remifentanil used in the two groups are lacking as well. In our opinion, it is difficult to homogenize administration of two opioid drugs between groups, because sevoflurane has intrinsic analgesic property whereas propofol does not. This may constitute a bias on the homogeneity between groups. It has been demonstrated that both fentanyl and remifentanil may exert cardioprotective effects by both preconditioning and reducing the cardiovascular stress, especially for remifentanil,6,7 so, their administration in general anesthesia could contribute to cardioprotective effects of two anesthesia methods. This further makes interpretation of their results difficult. Third, dopamine or noradrenaline was given intravenously at the discretion of the attending anesthesiologist to maintain mean artery pressure, and hemodynamic alterations during surgery were not significantly different between groups. However, the authors did not provide and compare the percent of patients with vasopressor use, the time of vasopressor use, and the total vasopressor dosage administered during the surgery. In patients undergoing open infrarenal abdominal aortic aneurysm repair, vasopressor use during the aorta cross-clamp has been identified as an independent risk factor of postoperative complications including myocardial infarction.8 We are concerned that their results would have been biased by these confounders. Finally, only one troponin measurement on the first postoperative day was performed for assessment of myocardial injury. In traditional clinical practices, perioperative cardiac adverse events in noncardiac surgery patients have indeed been emphasized more in the more early postoperative stage.9 However, Barbagallo et al.10 showed that in patients undergoing major vascular surgery, serum troponin reached the peak level on the third postoperative day, regardless of whether or not patients developed myocardial infarction. In 100 high-risk patients undergoing major noncardiac surgery, Mangano et al.11 monitored myocardial ischemia during the postoperative first week and found that myocardial ischemia was most severe during the early (days 0–3) versus late (days 4–7) postoperative period, 284 versus 153 episodes. Furthermore, the greatest severity occurred on the third postoperative day, 109 episodes. Similarly, in high-risk patients undergoing noncardiac surgery, Martinez et al.12 observed that perioperative cardiac injury detected by serum troponin continued to occur frequently after surgery, and serial monitoring of serum troponin on postoperative days 1, 2, and 3 provided the strategy with the highest diagnostic yield for surveillance of myocardial infarction. Accordingly, we would like to accentuate the importance of prolonging the monitoring period after surgery in noncardiac surgery patients. Also, we believe that if the authors had measured serum troponin in the more late postoperative periods, especially in the first 3 days after surgery, a more persuasive result would have been presented.

Assessing Independent Effects of Anemia and Transfusion on Late Mortality

In a retrospective analysis, Engoren and colleagues [1] showed that the anemia–transfusion interaction was associated with an increased risk of late mortality after coronary artery bypass graft surgery. The combined mortality risk of anemia and transfusion was nearly triple that of the nonanemic patient not receiving a transfusion. Furthermore, mortality risk associated with transfusion was increased in anemic patients compared with that in nonanemic patients. However, in this study 70 of the 922 operative survivors (8%) are dead in a long follow-up period, with a median duration of 2.45 years (interquartile range, 1.36 to 3.45 years). It is generally believed the mortality related to the surgery and anesthesia lasts only a month [2]. Thus, an important question is whether there is really a causal relation of perioperative anemia and transfusion with late mortality. Also, a limitation of this study is lack of evaluation for the association of perioperative anemia and transfusion with early mortality, which is more related to surgery and anesthesia than late mortality [2]. In general, early mortality after coronary artery bypass graft surgery is low [3]. In the longer term, the decline in patient survival most likely represents the natural process of aging [2]. In this study, patients who died are older and are more likely to have comorbidities. In our view, no matter how refined the adjustment is for differences in preoperative health status and comorbidities, it is never possible to ensure a complete adjustment for differences between decedents and survivors. Furthermore, Westenbrink and associates [4] demonstrate that postoperative anemia is common and frequently persists for months after coronary artery bypass graft surgery. When postoperative hemoglobin level is considered as a continuous variable, every 1 mg/dL decrease in hemoglobin level is associated with a 13% increase in adverse cardiovascular events and a 22% increase in all-cause mortality. Thus, statistical association of perioperative anemia and transfusion with late mortality in this study does not prove causality. We argue that late mortality more likely is attributable to the natural process of health status and pathologic developments of relevant morbidities.

Is Hydroxyethyl Starch 130/0.4 Safe for the Kidney in Noncardiac Surgical Patients?

Anesthesiology, V 123 • No 2 481 August 2015 To the Editor: The title of the publication by Kancir et al.1 implies lack of nephrotoxicity associated with the use of either 6% hydroxyethyl starch 130/0.4 or 0.9% NaCl during hip arthroplasty. The primary outcome variable was urinary concentrations of neutrophil gelatinase–associated lipocalin (u-NGAL). For all observation points, u-NGAL concentrations are reported as absolute and as values adjusted for creatinine (table 3). However, at the time of the highest u-NGAL concentrations (i.e., at discharge; observation point “urine 4”), values of neither creatinine clearance (table 3) nor plasma creatinine concentration (table 4) are provided. The authors describe the postoperative u-NGAL concentrations as only “slightly increased” and remaining “well below” the threshold of 100 ng/ml, considered to reflect acute kidney injury. However, at the time of patient discharge, median u-NGAL concentrations had increased 9to 11-fold over baseline values, and the 75% quartile values of u-NGAL at discharge were 160.5 and 116.3 ng/ml in the hydroxyethyl starch and NaCl groups, respectively (table 3). This indicates that several patients of each group had u-NGAL concentrations well above the critical concentration of 100 ng/ml, reflecting the development of some degree of nephrotoxicity. The authors mention in a somewhat passing fashion that their use of chloride-rich solutions may have contributed to the transient increases in u-NGAL concentrations. Infusion of 2 l of 0.9% NaCl in healthy individuals was associated with a 40% decrease of renal blood flow velocity and renal cortical tissue perfusion.2 This was accompanied by a mean increase in serum chloride concentrations from initially 103 to 108.5 mmol/l within 60 min of starting the infusion. Additional evidence supports the adverse renal effects of hyperchloremic solutions.3–5 Therefore, administration of hyperchloremic solutions might well have contributed to the clinically relevant increases in u-NGAL concentrations in some patients observed by Kancir et al.1 There are no large prospective clinical studies clearly documenting an adverse effect of perioperative administration of hyperchloremic solutions on outcome. Nevertheless, intraoperative infusion of hyperchloremic 0.9% NaCl carries a high potential of inducing hyperchloremic metabolic acidosis,6 and acute hyperchloremia and hyperchloremic acidosis have numerous adverse effects.7 It may thus be prudent to avoid the perioperative administration of hyperchloremic solutions altogether whenever possible. Competing Interests

Should videolaryngoscopes be as first choice for endotracheal intubation during cardiorespiratory resuscitation

In their article evaluating feasibility of GlideScope® videolarynoscope for endotracheal intubation (ETI) during cardiopulmonary esuscitation (CPR) in 71 emergency patients, Park et al.1 showed hat first ETI attempt was successful in 66 cases (93%), and median ime required for first successful ETI attempt was 41.5 s. Their esults suggest the potential of using a videolaryngoscope for ETI n CPR patient, but their statement in discussion that this study upports the use of a videolaryngoscope for ETI during CPR should e inconclusive, because a single cohort study with observational esigns cannot provide high-level evidence for clinical decisionarking. Just like the authors have mentioned in introduction, vailable evidences supporting the benefits of using a videolarynoscope during CPR are mostly from manikin studies, rather than andomized control clinical trials, which are widely accepted as he gold standard for evaluation of any treatment. Because the imulated airway scenes cannot represent real clinical situations, anikin studies often reveal results that are impossible to interret or even conflict with subsequent human studies. For example, manikin study simulating CPR shows that the Airwayscope is uperior to the direct laryngoscope in intubation time, success rate nd difficulty of intubation.2 However, in a randomized controlled linical trial including 109 patients primarily with prehospital cariac arrest, the Airwayscope does not show superior efficacy to he direct laryngoscope. Moreover, initial intubation with the Airayscope fails in 20 cases but is followed by successful intubation ith the direct laryngoscope.3 Of note, oral blood, vomitus or secretions, which frequently ccur in CPR patients,3 may become obstacles of using a videoaryngoscope, because a single drop of blood or smear of secretion r vomitus on the lens can completely obliterate the videolarynoscopic view.4 When the videolaryngoscope’s lens is obscured, evice must be removed and cleaned. Even if oral cleaning is perormed before intubation, vomitus or secretions regurgitated from he esophagus or trachea due to increased intra-thoracic pressure rom chest compressions can recur during intubation. Moreover, it s difficult or even impossible to remove the oral contaminations ith flexible suction catheters under videolaryngoscopy, as these atheters do not follow the angle of the sharply curved blade and annot be brought into a position to be effective.4 Obviously, all

Association between Intraoperative Ventilation Strategies and Postoperative Pulmonary Outcomes in Surgical Patients

To the Editor: In a small-sample, randomized, clinical trial comparing standard and protective ventilation strategies in patients with normal lung function undergoing elective laparotomy, Severgnini et al.1 showed that a protective ventilation strategy during surgery improved the postoperative respiratory function and reduced the clinical signs of postoperative pulmonary infection. Other than strict inclusion and exclusion criteria of patients, the authors should also be applauded for trying to control most of preoperative and intraoperative risk factors that may affect the postoperative respiratory function and pulmonary complications, such as age, body mass index, American Society of Anesthesiologists classification, history of smoking, type of surgery, anesthetic protocol, antibiotic prophylaxis, blood transfusion, intraoperative complications, uses of postoperative analgesia and physiotherapy, and many more.2,3 However, to differentiate the effect of one factor on postoperative pulmonary outcomes, all of the other factors have to be standardized. In this study, several important issues were not addressed. First, perioperative hemoglobin levels are not included in data analysis. Preoperative anemia is common among surgical patients. In a previous study including 227,425 noncardiac surgery patients, 69,229 patients (30.4%) have preoperative anemia, of whom 57,870 (83.6%) are mild anemic and 11,359 (16.4%) are moderate-to-severe anemic.4 It has been shown that preoperative anemia is independently associated with the postoperative pulmonary complications.5 Furthermore, low preoperative and postoperative hemoglobin levels are associated with increased perioperative mortality, increased postoperative pneumonia, and increased hospital length of stay.6 Second, there was no mention of serum albumin level. A low serum albumin level has been shown to be an important predictor of pulmonary complications after major noncardiac surgery.7 According to the guideline of the American College of Physicians on risk assessment for and strategies to reduce perioperative pulmonary complications for patients undergoing noncardiothoracic surgery, serum albumin should be measured in all patients who are clinically suspected of having hypoalbuminemia and in those with one or more risk factors of postoperative pulmonary complications.2 Third, the authors did not describe use of nasogastric tubes although 63 to 71.4% of the study population underwent gastrointestinal surgery. A meta-analysis examined evidence from studies regarding selective and routine use of nasogastric tube for gastrointestinal decompression after elective laparotomy and showed that patients receiving selective use of nasogastric tube had a significantly decreased incidence of postoperative pneumonia and atelectasis.8 measurements in patients undergoing laparotomy.3 There is a significant negative correlation between perioperative spirometric tests and obesity. The reduction in postoperative lung volumes was significantly greater in obese patients than in normal-weight patients. Also, surgery with general anesthesia may reduce lung volumes and this effect may be greater in the obese patients.4 So, we think the authors should give the information about the proportion of the obese patients in the two groups. Second, the authors state that most patients underwent epidural anesthesia at the T8 to T12 level before general anesthesia and received continuous analgesia after surgery. High thoracic perioperative epidural anesthesia was shown to decrease spirometric measurements by blocking intercostal muscle innervation.5 Even if low concentrations of local anesthetics are used, the sensory levels of epidural anesthesia extending from approximately T4 to L1 are likely to be accompanied by some degree of muscle paralysis.6 It is more likely to block the muscles of the abdominal wall (innervation T6–L1). Even a subtle decrease in abdominal muscle tone will affect dynamic parameters. To avoid the influence of the epidural anesthesia on spirometric measurements, we think it is necessary to perform a pulmonary functional test after the epidural anesthesia. Or else, the authors should give the information about the epidural anesthesia including the dose of the local anesthetics, the direction of the epidural catheter, and the plane of the epidural anesthesia.