Jacques Somma

Dexmedetomidine pharmacodynamics: Part II: Crossover comparison of the analgesic effect of dexmedetomidine and remifentanil in healthy volunteers.

Background:Dexmedetomidine is a highly selective &agr;2-adrenoceptor agonist used for short-term sedation of mechanically ventilated patients. The analgesic profile of dexmedetomidine has not been fully characterized in humans. Methods:This study was designed to compare the analgesic responses of six healthy male volunteers during stepwise target-controlled infusions of remifentanil and dexmedetomidine. A computer-controlled thermode was used to deliver painful heat stimuli to the volar side of the forearms of the subjects. Six sequential 5-s stimuli (ranging from 41° to 50°C) were delivered in random order. The recorded visual analog scale was used to fit an Emax model. Results:Compared to baseline, remifentanil infusions resulted in a right shift of the sigmoid curve (increased T50, the temperature producing a visual analog scale score of 50% of the maximal effect, from 46.1°C at baseline to 48.4° and 49.1°C during remifentanil infusions) without a change of the steepness of the curve (identical Hill coefficients &ggr; during baseline and remifentanil). Compared to baseline, dexmedetomidine infusions resulted in both a right shift of the sigmoid curve (increased T50 to 47.2°C) and a decrease in the steepness of the curve (decreased &ggr; from 3.24 during baseline and remifentanil infusions to 2.45 during dexmedetomidine infusions). There was no difference in the pain responses between baseline and after recovery from remifentanil infusions (identical T50 and &ggr;). Conclusion:As expected, dexmedetomidine is not as effective an analgesic as the opioid remifentanil. The difference in the quality of the analgesia with remifentanil may be a reflection of a different mechanism of action or a consequence of the sedative effect of dexmedetomidine.

Population Pharmacodynamics of Midazolam Administered by Target Controlled Infusion in SICU Patients after CABG Surgery

Background Midazolam is used commonly for sedation in the surgical intensive care unit. A suboptimal dosing regimen may lead to relative overdosing, which could result in delayed extubation and increased cost. This multicenter trial characterized midazolam pharmacodynamics in patients recovering from coronary artery bypass grafting. Methods Three centers enrolled 90 patients undergoing coronary artery bypass grafting. All patients received sufentanil and midazolam via target‐controlled infusion. After surgery, midazolam was titrated to a Ramsay sedation score of 5 for 2 h and then decreased to maintain a sedation score of 3 or 4 for at least another 4 h. Pharmacodynamic parameters were derived using NONMEM. The model was cross‐validated to test performance. Results The probability of a given level of sedation was related to the midazolam concentration by this equation: P(Sedation >or= to ss) = Cn/(C (n) + C50,ssn), where ss is the sedation score, C is the sum of the midazolam concentration and a term reflecting the dissipating effect of anesthesia: C = [midazolam] + [small theta, Greek] x e‐Kt, where [small theta, Greek] = 256 ng/ml and K = 0.19 h‐1. C50,ss values for Ramsay scores of 2 to 6 were 5.7, 71, 171, 260, and 659 ng/ml, respectively. The model predicted 57% of the data points correctly and 88% within one sedation score. Conclusions Despite previous reports of high interindividual variability in midazolam pharmacodynamics in patients in the surgical intensive care unit, these cross‐validation results suggest that, when midazolam is administered using a target‐controlled infusion device, the level of sedation can be predicted within 1 sedation score in 88% of patients based on the target midazolam concentration and the time since the conclusion of the anesthetic.

Population pharmacokinetics of midazolam administered by target controlled infusion for sedation following coronary artery bypass grafting.

Background Midazolam is commonly used for short‐term postoperative sedation of patients undergoing cardiac surgery. The purpose of this multicenter study was to characterize the pharmacokinetics and intersubject variability of midazolam in patients undergoing coronary artery bypass grafting. Methods With institutional review board approval, 90 consenting patients undergoing coronary artery bypass grafting were enrolled at three study centers. All subjects received sufentanil and midazolam via target‐controlled infusions. After operation, midazolam was titrated to maintain deep sedation for at least 2 h. It was then titrated downward to decrease sedation for a minimum of 4 h more and was discontinued before tracheal extubation. Arterial blood samples were taken throughout the study and were assayed for midazolam and 1‐hydroxymidazolam. Midazolam population pharmacokinetic parameters were estimated using NONMEM. Cross‐validation was used to estimate the performance of the model. Results The pharmacokinetics of midazolam were best described by a simple three‐compartment mammillary model. Typical pharmacokinetic parameters were V1 = 32.2 1, V2 = 53 1, V3 = 245 1, Cl1 = 0.43 1/min, Cl2 = 0.56 1/min, and Cl3 = 0.39 1/min. The calculated elimination half‐life was 15 h. The median absolute prediction error was 25%, with a bias of 1.4%. The performance in the cross‐validation was similar. Midazolam metabolites were clinically insignificant in all patients. Conclusions The intersubject variability and predictability of the three‐compartment pharmacokinetic model are similar to those of other intravenous anesthetic drugs. This multicenter study did not confirm previous studies of exceptionally large variability of midazolam pharmacokinetics when used for sedation in intensive care settings.

The desaturation response time of finger pulse oximeters during mild hypothermia

Pulse oximeters may delay displaying the correct oxygen saturation during the onset of hypoxia. We investigated the desaturation response times of pulse oximeter sensors (forehead, ear and finger) during vasoconstriction due to mild hypothermia and vasodilation caused by glyceryl trinitrate. Ten healthy male volunteers were given three hypoxic challenges of 3 min duration under differing experimental conditions. Mild hypothermia increased the mean response time of finger oximeters from 130 to 215 s. Glyceryl trinitrate partly offset this effect by reducing the response time from 215 to 187 s. In contrast, the response times of the forehead and ear oximeters were unaffected by mild hypothermia, but the difference between head and finger oximeters was highly significant (p < 0.0001). The results suggest that the head oximeters provide a better monitoring site for pulse oximeters during mild hypothermia.

A customized stylet for GlideScope® insertion of double lumen tubes

To the Editor, The double lumen tube (DLT) is the airway of choice to establish and maintain lung isolation. However, it can be challenging to secure the airway with a DLT in patients with a difficult airway because DLTs are larger, more rigid, and more difficult to place into the trachea than single lumen tubes. Recently, a high level of success was achieved using the GlideScope (GLS) to assist in positioning a single lumen tube (SLT) in situations where the airway was considered or proven to be difficult. The GLS has also been advanced for DLT placement in patients with difficult airways. In collaboration with Verathon Medical Canada ULC, we recently designed a new semi-rigid intubating stylet, the GlideRite DLT Stylet (GR-DLT-S) (Figure), which can be used for primary DLT intubation with the GLS. The GlideRite DLT Stylet (Verathon Medical Canada ULC, Burnaby, BC, Canada) is a reusable device which has been commercially available since March 2010 (In Canada, information on the device is available from CAREstream Medical Ltd., Langley, BC, Canada). We undertook a preliminary study to observe the efficiency of the GR-DLT-S for primary insertion of a DLT with the GLS in patients presenting a normal upper airway. After obtaining Research Ethics Board approval from our institution, 50 adult patients scheduled for thoracic surgery and requiring lung isolation were enrolled after written informed consent. Exclusion criteria included patients with anticipated difficult bag-mask ventilation of the lungs or anticipated difficult tracheal intubation according to the standard criteria, such as Mallampati class [ 3. Following application of routine monitors, pre-oxygenation, induction, and paralysis, tracheal intubation with the DLT was undertaken using both the GLS and the GR-DLT-S. Forty-nine (98%) patients received tracheal intubation using the combination of DLT/GLS/GR-DLT-S. The mean time required for intubation was 46.3 (32.3) sec. The number of attempts was one in 37 patients (74%), two in 11 patients (22%), and three in one patient (2%). None of the subjects experienced complications associated with DLT insertion. Three publications have described the use of the Glidescope to facilitate DLT tracheal intubation. In 2005, Hernandez et al. described the first use of the GLS to introduce a DLT. In 2008, Chen et al. described a failure to insert a DLT with the GLS. They used the GLS to introduce a SLT, and afterwards, they used a tube exchanger to replace the SLT with a DLT, also with the assistance of the GLS. Finally, Bustamante et al. described a case report where bending the malleable stylet and sequential rotation of the DLT enabled them to introduce the DLT successfully. These authors reported a dozen successful cases using this technique. Over the past five years, we had several cases where we failed to intubate the trachea with a DLT using a similar method. The failed cases involved patients with little room to maneuver the DLT due to a large tongue or a small mouth opening. In these cases, the malleable stylet was not sufficiently rigid to maintain the optimal tube curvature. Since the introduction of the GR-DLT-S, tracheal intubation with the DLT has been successful using this new device in more than 15 patients with either a proven or an anticipated difficult airway. In conclusion, based on our initial experience, we suggest that the GR-DLT-S is effective when used in J. S. Bussieres, MD (&) F. Martel, MD J. Somma, MD S. Morin, MSc N. Gagne, PhD RRT Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec City, QC, Canada e-mail: jean.bussieres@anr.ulaval.ca

Changes in hematocrit based on incremental blood sampling: mathematical models perform poorly.

PurposeExcessive blood sampling, with its inherent risks, is of growing concern among clinicians. We performed this study to measure the changes in hematocrit (Hct) during a laboratory investigation where multiple blood samples are collected. The performance of a simple mathematical model, used in clinical practice to predict Hct changes, is evaluated.MethodsEight healthy male volunteers participated in this study. The equation Hctf = Hcti*(EBV-BL)/EBV is used to predict changes in Hct. Where Hctf and Hcti are, respectively, the final and initial Hct, EBV is the estimated blood volume and BL is the blood loss.ResultsThirty-five pharmacokinetic samples per subject were collected totalling 314 mL of BL.The Hct decreased from 44.2% ± 2.2% to 39.9% ± 2.5% (P = 0.001). On average, model predictions tended to have a discrete tendency to underestimate the Hct changes (-0.5% points of bias). While the predictions of the Hct were very accurate in 50% of the subjects, the discrepancy of the Hct predictions was clinically significant in the other 50% of the subjects.ConclusionConsistent with the model prediction, this study demonstrated a significant reduction in the Hct values in healthy subjects undergoing incremental phlebotomy. On average, the model successfully predicted the decrease in Hct. However, the inter- and intra-individual variabilities in the Hct changes are clinically significant. In clinical settings, which are not well controlled environments, the variability is likely to be greater and the clinical use of the model cannot replace the need to monitor the Hct.ObjectifLes échantillons sanguins excessifs, et leurs risques inhérents, préoccupent de plus en plus les cliniciens. Nous avons mesuré les modifications de l’hématocrite (Hct) au cours d’une investigation en laboratoire où de multiples échantillons sanguins sont prélevés. La performance d’un modèle mathématique simple, qui prédit les changements de l’Hct en clinique, est évaluée.MéthodeHuit hommes volontaires en santé ont participé à l’étude. L’équation Hctf = Hct*(VSE-PS)/VSE sert a prédire les changements de l’Hct où Hct et Hct sont respectivement l’Hct final et initial, VSE est le volume sanguin estimé et PS est la perte sanguine.RésultatsTrente-cinq échantillons pharmacocinétiques par sujet ont été prélevés pour un total de 314 mL de PS. L’Hct a diminué de 44,2 % ± 2,2 % à 39,9 % ± 2,5 % (P = 0,001). Les prédictions du modèle présentaient en moyenne une tendance discrète à sous-estimer les modifications de l’Hct (-0,5 % de biais). Les prédictions de l’Hct ont été très exactes chez 50 % des sujets, mais la divergence dans les prédictions était cliniquement significative chez les autres 50 %.ConclusionL’étude a démontré, conformément au modèle de prédiction, une réduction significative des valeurs de l’Hct chez des sujets sains qui subissent une phlébotomie incrémentielle. En moyenne, le modèle a pu prédire la baisse de l’Hct. Cependant, les variations interindividuelles et intra-individuelles de modification de l’Hct sont cliniquement significatives. En clinique, ce qui n’est pas un environnement bien conträlé, la variabilité risque d’être plus grande et l’usage clinique du modèle ne peut remplacer la nécessité du moniteur d’Hct.

Avoidable tracheal injury using a double-lumen endotracheal tube: a case report

To the Editor, The incidence of iatrogenic tracheobronchial injuries after intubation is estimated to be 1/20,000. Double-lumen endotracheal tubes (DLT) were placed in half of such injuries. We report the presentation and management of a DLT-associated tracheal injury. A 63-yr-old female, who consented to this report, was scheduled for video-assisted thoracoscopic right upper lobectomy. After induction of general anesthesia, a 37-Fr left DLT was inserted with a GlideScope and GlideRite DLT Stylet (Verathon Inc, Oakville, ON, Canada). The guide was withdrawn after the tip of the tube had passed the vocal cords. The DLT was blindly advanced 1-2 cm into the trachea, rotated 90 counter-clockwise, and then advanced further until resistance was felt. Flexible bronchoscopy performed in both tracheal and bronchial lumens was reported as normal. The patient was positioned in the left lateral decubitus position with bronchoscopy again used to confirm the DLT position. At pleural opening, lung isolation was found to be inadequate. The bronchoscope was reinserted in the tracheal lumen and the tube was withdrawn into the trachea. At this point, the anesthesiologist realized that both orifices of the DLT had been initially inserted in the right mainstem bronchus. The DLT was turned 90 counter-clockwise and reinserted into the left main bronchus under bronchoscopic guidance. Neither blood nor tracheal laceration was noted. After surgery, the patient was easily re-intubated with a single-lumen 7.5-mm internal diameter endotracheal tube. During subsequent bronchoscopy, we discovered a 4-cmlong tracheal laceration on the left side of the trachea, at the junction of the posterior (pars membranacea) and cartilaginous aspect. Computed tomography (CT) scan revealed a 39 mm 9 22 mm posterior tracheal laceration, 11 mm from the carina (Figure a), without air or blood in the mediastinum. The team opted for conservative management and the patient was extubated without incident. The following day, an oral contrast CT scan confirmed the integrity of the esophagus. Bronchoscopy five days after surgery showed fibrinous tissue in the wound and the esophagus bulging into the trachea with coughing. Two months after surgery, bronchoscopy showed healing by a well-defined scar (Figure b). Blind insertion of a DLT is a common technique; however, misplacement of a left DLT in the right mainstem bronchus was reported in 48 (4.2%) of 1,135 consecutive patients in a single centre study. Subsequent manipulations of DLTs are another risk factor for tracheal trauma. It is the authors’ opinion that moving a DLT while the patient is in the lateral decubitus position is more difficult and traumatic and we suspect that was the mechanism of the injury described here. We advocate the use of flexible bronchoscopy through the bronchial lumen for the primary positioning of both left and right DLTs. This technique minimizes misinterpretation of bronchial anatomy that may occur when DLTs are advanced blindly. Case series support conservative management of tracheal lacerations; a systematic review describes indications for conservative management. Healing of such injuries can be expected to take up to four weeks. Airway stenting has been recently suggested for J. Lemay, MD M. Conti, MD J. Somma, MD, BEng L. Vigneault, MD, BSc J. S. Bussières, MD, FRCPC (&) Institut universitaire de cardiologie et de cardiologie de Québec, Québec, QC, Canada e-mail: jbuss@criucpq.ulaval.ca

Modified and Newly Designed Right-sided Double-lumen Endobronchial Tubes Are Complementary

To the Editor:—We read with great interest the case report on the application of a newly designed right-sided, double-lumen endobronchial tube (R-DLT) in patients with a very short right mainstem bronchus. However, in citing our work on the improvement of the endobronchial positioning of the R-DLT, Hagihira et al. stated that we modified the design of the bronchial cuff and that these changes seem to offer little improvement. This statement is inconsistent with our published manuscript which demonstrates, on a randomized series of 80 patients, that the modified enlarged area of the lateral orifice (and not the bronchial cuff as stated by Hagihira et al.) improve the success rate of final positioning from 74 to 97% with a P 0.0109. These two new versions of the R-DLT are not intended to solve the same problem, but the final objective, improvement of the use of R-DLT, is similar. We thank Dr. Hagihira for this interesting case report. While this new R-DLT may become a useful tool for thoracic anesthesiologists, we would first encourage them to validate its use with a randomized study.