Correspondence
auscultating air entry over the epigastrium, the bowl portion of the PLM was once again tightly approximated to the shaft and gently introduced into the oral cavity from the right side by railroading over the suction catheter (Fig. 1). With minimal manipulation, the laryngeal mask airway could be introduced. Suction catheter was removed and breathing circuit was attached (Figure S2). With just 3-ml air to inflate the laryngeal mask airway cuff, adequate spontaneous respiration was noted by the movement of the reservoir bag and capnographic curves. Subsequently, the patient was maintained on 1–3% sevoflurane in a mixture of 50% nitrous oxide in oxygen on spontaneous breathing. The attending anesthesiologist attempted fiberscopy through the laryngeal mask airway but failed as the laryngeal mask airway was noted to be poorly positioned, a finding noted by others also (4). Throughout this period, patient had been breathing spontaneously receiving sevoflurane in oxygen via face mask between attempts. Oxygen saturation remained between 98 and 100% and heart rate ranged between 113 and 146/min. As the patient has to come for multiple surgeries over the next few weeks, it was decided to perform surgical tracheostomy prior to the release of various contractures in stages (Figure S3). Since then, the patient has been anesthetized uneventfully several times using tracheostomy as an airway. This case report highlights the fact that a distorted airway anatomy secondary to scarring may impair both
mask ventilation and much advocated fiberoptic tracheal intubation. In addition, traditional rescue methods such as the laryngeal mask airway may fail using the conventional approach. The key to success is adequate planning, preparation, and the ability to improvise to suit the occasion as demonstrated by successful catheterguided placement of the laryngeal mask airway in this patient. Conflict of interest No conflicts of interest declared. Rashid M. Khan, Naresh Kaul, Haris Aziz, Hajar M. S. Al-Mughairi & Wala A. A. Ahmed Al Ajmi Department of Anesthesia & ICU, Khoula Hospital, Muscat, Sultanate of Oman Email: [email protected] doi:10.1111/pan.12292
Supporting information Additional Supporting Information may be found in the online version of this article: Figure S1 (a & b) Frontal and lateral view of the post burn contractures over face, neck and chest. Figure S2 Laryngeal mask airway in place. Figure S3 Tracheostomy tube securely connected to the breathing circuit.
References 1 Caruso TJ, Janik LS, Fuzaylov G. Airway management of recovered pediatric patients with severe head and neck burns: a review. Pediatr Anesth 2012; 22: 462–468. 2 Maclean J, Tripathy D, Parthasarathy S et al. Comparative evaluation of gum-elastic bougie and introducer tool as aids in positioning of
ProSeal laryngeal mask airway in patients with simulated restricted neck mobility. Indian J Anaesth 2013; 57: 248–252. 3 Joffe AM, Schroeder KM, Shepler JA et al. Validation of the unassisted, gum-elastic bougie-guided, laryngeal mask airwayProSealTM placement technique in anaesthe-
tized patients. Indian J Anaesth 2012; 56: 255– 258. 4 Latorre F, Eberle B, Weiler N et al. Laryngeal mask airway position and the risk of gastric insufflation. Anesth Analg 1998; 86: 867–871.
Intranasal clonidine pharmacokinetics SIR—The intranasal route is becoming increasingly popular for drug delivery in children because needles can be avoided and the ‘first-pass’ effect that is associated with flow-dependent drugs given orally may be reduced. The pharmacokinetics of nasal clonidine (4 mcgkg1) have been published using estimates of 340
elimination half-life (t1/2) and time (Tmax) to maximum concentration (Cmax) (1). These parameters are used by regulatory authorities to determine the bioequivalence of generic medicines to originator medicines. However, efforts to estimate a mean Tmax or Cmax may be limited by sampling density about © 2014 John Wiley & Sons Ltd Pediatric Anesthesia 24 (2014) 339–357
Correspondence
the presumed Tmax. These confounded parameters are unsuitable for simulating time–concentration profiles after an intranasal dose; alternative parameters such as nasal bioavailability (F), absorption half-time (Tabs), lag time (Tlag), clearance (CL), between compartment clearance (Q), central volume (V1) and peripheral (V2) volumes of distribution adequately describe a two-compartment model. The extent to which a drug is absorbed is known as the bioavailability (F), and this in turn is dependent upon the fraction of drug that is absorbed into the portal vein (f) and the extraction ratio (ER). The bioavailability can be calculated using the equation F = f • (1-ER). Intravenous bioavailability is assumed as unity. The rate of drug absorption is dependent upon whether absorption is a zero-order or first-order process. In zero-order drug absorption, a constant amount of the drug is absorbed, while in first-order drug absorption, a constant fraction of the drug is absorbed. First-order drug absorption is assumed for many oral formulations including clonidine where the drug is administered as a solution or dissolves rapidly. This is expressed using a proportionality constant (Ka); however, it may be easier to describe using the absorption half-time (Tabs) where: Tabs ¼ Lnð2Þ=Ka Individual time–concentration profiles from this intranasal study (1) were pooled with data from studies investigating pharmacokinetics after oral (2) and intravenous (3–5) administration of clonidine. A total of 66 children were included in the final analysis. A two-compartment linear model was used to fit data. Population parameter estimates were obtained using nonlinear mixed-effects models (NONMEM VII; Globomax LLC, Hanover, MD, USA), and estimates were standardized to a 70-kg adult using allometric size models. Population parameter estimates (between subject variability) for nasal clonidine were CL 18.3 (31.4%) l h1.70 kg1, V1 80.2 (73.7%) l 70 kg1, Q 121 (30.8%) l h1.70 kg1, V2 114 (52.0%) l.70 kg1, Tabs 0.94 (50.0%) h, Tlag 0.127 (68.9%) h. Bioavailability (F) was 1. CL at birth was 4.61 l h1.70 kg1 and this matured to reach 90% of the adult CL by a postmenstrual age of 165 weeks. Simulations of intravenous, nasal and oral clonidine can be seen in Figure 1. These parameter estimates can be used to predict Tmax and Cmax. The time of the peak concentration occurs when the rate of absorption is equal to the rate of elimination. Absorption is more than 90% complete after 4 absorption half-times. A crude method of determining
© 2014 John Wiley & Sons Ltd Pediatric Anesthesia 24 (2014) 339–357
Figure 1 Concentration-time profiles for clonidine administered intravenously, orally and intranasally.
the Tmax is by multiplying the Tabs by 3. Nasal clonidine has a larger Tabs than that estimated for oral clonidine (Tabs 0.45 h), and this is reflected in the Tmax being observed at a later time after the administration of nasal clonidine. Oral clonidine has a lower bioavailability (F = 0.55) than nasal clonidine (F = 1); thus, a lower Cmax is observed compared with nasal clonidine as seen in Figure 1 (2). The equilibrium rate constant (Keo) for plasma to effect compartment equilibration remains unknown for clonidine, but simulation demonstrates that there will be delayed onset and offset of sedative effect after nasal administration compared with oral administration. The choice of administration route will depend on the clinical scenario; the nasal route might not always be preferable. Although the route is often chosen solely for the ease of administration, the bioavailability and kinetics must also be borne in mind because these all impact on dose, time of onset and time of offset in ways that might not be immediately obvious. Conflict of interest No conflicts of interest declared. Lee Blackburn1, Nicole Almenrader2, Peter Larsson3 & Brian J. Anderson1 1 Department of Anaesthesiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand 2 Department of Anaesthesia and Intensive Care, Policlinico Umberto I, Rome, Italy 3 Department of Physiology and Pharmacology, Section of Anaesthesiology & Intensive Care, Karolinska Institutet, Stockholm, Sweden Email: [email protected] doi:10.1111/pan.12297
341
Correspondence
References 1 Almenrader N, Larsson P, Passariello M et al. Absorption pharmacokinetics of clonidine nasal drops in children. Pediatr Anesth 2009; 19: 257– 261. 2 Larsson P, Nordlinder A, Bergendahl HT et al. Oral bioavailability of clonidine in children. Pediatr Anesth 2011; 21: 335–340.
3 Potts AL, Larsson P, Eksborg S et al. Clonidine disposition in children; a population analysis. Pediatr Anesth 2007; 17: 924–933. 4 Lonnqvist PA, Bergendahl H. Pharmacokinetics and haemodynamic response after an intravenous bolus injection of clonidine in children. Paediatr Anaesth 1993; 3: 359–364.
5 Bergendahl HT, Eksborg S, Lonnqvist PA. Low-dose intravenous clonidine in children: plasma concentrations and haemodynamic response. Acta Anaesthesiol Scand 1997; 41: 381–384.
Supraclavicular subclavian vein catheterization is still forgotten
SIR—We read the excellent article, A review of 5434 percutaneous pediatric central venous catheters inserted by anesthesiologists, by Malbezin et al. (1) with interest. Concerning the high number of patient, we are surprised that the supraclavicular subclavian vein (SSV) approach for central venous catheterization (CVC) was not used by authors (specifically trained pediatric anesthesiologist for CVC) in any of the pediatric patients. The use of SSV approach for central venous cannulation is gradually increasing in both adult and pediatric patients (2–4). It is known that SSV approach for CVC is successfully used by pediatric anesthesiologists in pediatric patients in author’s country (2). Why the authors did not choose SSV approach for CVC in any pediatric patient? Yoffa (5) described a SSV approach of CVC, advocating it as a safe method with low rate of complication in 1965. Patrick et al. (6) mentioned that SSV approach for CVC is “the forgotten central line” in 1999. Cunningham and Gallmeier (7) mentioned that “supraclavicular approach for central venous cannulation is safer, simpler, speedier method”. We think that the SSV approach is rather safe and may be considered as the first choice of CVC method whenever a central venous route is required. We have been using SSV approach as the primary alternative for CVC in both adult and pediatric patient groups. The vast majority of the inserted central venous lines by Malbezin et al. (1) were tunnelled. The use of SSV approach has no disadvantages for tunnelled types of central venous lines. Rhondali et al. (2) used the SSV approach for CVC with or without tunnelled catheters in infants and stated that the tunnelization was much easier in subclavian vein than internal jugular vein. Simi-
342
larly, Guilbert et al. (4) also mentioned that the subclavian vein is easily accessed for tunnelization in infants in their study which revealed successful results with SSV approach. Rhondali et al. (2) consider the subclavian vein as a more favorable site for long-term CVC with a supraclavicular approach in pediatric patients to avoid compression of the central venous catheter between the first rib and clavicle. We have previously reported that the use of SSV approach for CVC has lower risk of catheter compression when compared with the infraclavicular approach of subclavian vein even after sternal retraction (3). The overall complication rate of jugular venous catheterization (JVC) was reported as 1.3% and regarded as favorable when compared with the literature by the author (1). Although very rare, it is a wellknown fact that the serious neurologic damage and death subsequent to cerebral infarct due to in advertent carotid artery puncture is a major complication of JVC. The use of SSV approach for CVC avoids this serious complication. Moreover, Guilbert et al. (4) mentioned that SSV approach for central venous cannulation is “safe, reliable, with few early complications” in pediatric patients. We think that the SSV approach for CVC is a safe and preferable method in pediatric patients due to their additional advantages including the ease of neck movement, medical dressing, and catheter care by medical staff in long-term catheter usage and an improved patient comfort. We have emphasized that using the SSV approach is a safe alternative for CVC in pediatric patients; therefore, we think that the SSV approach should not be forgotten for central venous cannulation.
© 2014 John Wiley & Sons Ltd Pediatric Anesthesia 24 (2014) 339–357
auscultating air entry over the epigastrium, the bowl portion of the PLM was once again tightly approximated to the shaft and gently introduced into the oral cavity from the right side by railroading over the suction catheter (Fig. 1). With minimal manipulation, the laryngeal mask airway could be introduced. Suction catheter was removed and breathing circuit was attached (Figure S2). With just 3-ml air to inflate the laryngeal mask airway cuff, adequate spontaneous respiration was noted by the movement of the reservoir bag and capnographic curves. Subsequently, the patient was maintained on 1–3% sevoflurane in a mixture of 50% nitrous oxide in oxygen on spontaneous breathing. The attending anesthesiologist attempted fiberscopy through the laryngeal mask airway but failed as the laryngeal mask airway was noted to be poorly positioned, a finding noted by others also (4). Throughout this period, patient had been breathing spontaneously receiving sevoflurane in oxygen via face mask between attempts. Oxygen saturation remained between 98 and 100% and heart rate ranged between 113 and 146/min. As the patient has to come for multiple surgeries over the next few weeks, it was decided to perform surgical tracheostomy prior to the release of various contractures in stages (Figure S3). Since then, the patient has been anesthetized uneventfully several times using tracheostomy as an airway. This case report highlights the fact that a distorted airway anatomy secondary to scarring may impair both
mask ventilation and much advocated fiberoptic tracheal intubation. In addition, traditional rescue methods such as the laryngeal mask airway may fail using the conventional approach. The key to success is adequate planning, preparation, and the ability to improvise to suit the occasion as demonstrated by successful catheterguided placement of the laryngeal mask airway in this patient. Conflict of interest No conflicts of interest declared. Rashid M. Khan, Naresh Kaul, Haris Aziz, Hajar M. S. Al-Mughairi & Wala A. A. Ahmed Al Ajmi Department of Anesthesia & ICU, Khoula Hospital, Muscat, Sultanate of Oman Email: [email protected] doi:10.1111/pan.12292
Supporting information Additional Supporting Information may be found in the online version of this article: Figure S1 (a & b) Frontal and lateral view of the post burn contractures over face, neck and chest. Figure S2 Laryngeal mask airway in place. Figure S3 Tracheostomy tube securely connected to the breathing circuit.
References 1 Caruso TJ, Janik LS, Fuzaylov G. Airway management of recovered pediatric patients with severe head and neck burns: a review. Pediatr Anesth 2012; 22: 462–468. 2 Maclean J, Tripathy D, Parthasarathy S et al. Comparative evaluation of gum-elastic bougie and introducer tool as aids in positioning of
ProSeal laryngeal mask airway in patients with simulated restricted neck mobility. Indian J Anaesth 2013; 57: 248–252. 3 Joffe AM, Schroeder KM, Shepler JA et al. Validation of the unassisted, gum-elastic bougie-guided, laryngeal mask airwayProSealTM placement technique in anaesthe-
tized patients. Indian J Anaesth 2012; 56: 255– 258. 4 Latorre F, Eberle B, Weiler N et al. Laryngeal mask airway position and the risk of gastric insufflation. Anesth Analg 1998; 86: 867–871.
Intranasal clonidine pharmacokinetics SIR—The intranasal route is becoming increasingly popular for drug delivery in children because needles can be avoided and the ‘first-pass’ effect that is associated with flow-dependent drugs given orally may be reduced. The pharmacokinetics of nasal clonidine (4 mcgkg1) have been published using estimates of 340
elimination half-life (t1/2) and time (Tmax) to maximum concentration (Cmax) (1). These parameters are used by regulatory authorities to determine the bioequivalence of generic medicines to originator medicines. However, efforts to estimate a mean Tmax or Cmax may be limited by sampling density about © 2014 John Wiley & Sons Ltd Pediatric Anesthesia 24 (2014) 339–357
Correspondence
the presumed Tmax. These confounded parameters are unsuitable for simulating time–concentration profiles after an intranasal dose; alternative parameters such as nasal bioavailability (F), absorption half-time (Tabs), lag time (Tlag), clearance (CL), between compartment clearance (Q), central volume (V1) and peripheral (V2) volumes of distribution adequately describe a two-compartment model. The extent to which a drug is absorbed is known as the bioavailability (F), and this in turn is dependent upon the fraction of drug that is absorbed into the portal vein (f) and the extraction ratio (ER). The bioavailability can be calculated using the equation F = f • (1-ER). Intravenous bioavailability is assumed as unity. The rate of drug absorption is dependent upon whether absorption is a zero-order or first-order process. In zero-order drug absorption, a constant amount of the drug is absorbed, while in first-order drug absorption, a constant fraction of the drug is absorbed. First-order drug absorption is assumed for many oral formulations including clonidine where the drug is administered as a solution or dissolves rapidly. This is expressed using a proportionality constant (Ka); however, it may be easier to describe using the absorption half-time (Tabs) where: Tabs ¼ Lnð2Þ=Ka Individual time–concentration profiles from this intranasal study (1) were pooled with data from studies investigating pharmacokinetics after oral (2) and intravenous (3–5) administration of clonidine. A total of 66 children were included in the final analysis. A two-compartment linear model was used to fit data. Population parameter estimates were obtained using nonlinear mixed-effects models (NONMEM VII; Globomax LLC, Hanover, MD, USA), and estimates were standardized to a 70-kg adult using allometric size models. Population parameter estimates (between subject variability) for nasal clonidine were CL 18.3 (31.4%) l h1.70 kg1, V1 80.2 (73.7%) l 70 kg1, Q 121 (30.8%) l h1.70 kg1, V2 114 (52.0%) l.70 kg1, Tabs 0.94 (50.0%) h, Tlag 0.127 (68.9%) h. Bioavailability (F) was 1. CL at birth was 4.61 l h1.70 kg1 and this matured to reach 90% of the adult CL by a postmenstrual age of 165 weeks. Simulations of intravenous, nasal and oral clonidine can be seen in Figure 1. These parameter estimates can be used to predict Tmax and Cmax. The time of the peak concentration occurs when the rate of absorption is equal to the rate of elimination. Absorption is more than 90% complete after 4 absorption half-times. A crude method of determining
© 2014 John Wiley & Sons Ltd Pediatric Anesthesia 24 (2014) 339–357
Figure 1 Concentration-time profiles for clonidine administered intravenously, orally and intranasally.
the Tmax is by multiplying the Tabs by 3. Nasal clonidine has a larger Tabs than that estimated for oral clonidine (Tabs 0.45 h), and this is reflected in the Tmax being observed at a later time after the administration of nasal clonidine. Oral clonidine has a lower bioavailability (F = 0.55) than nasal clonidine (F = 1); thus, a lower Cmax is observed compared with nasal clonidine as seen in Figure 1 (2). The equilibrium rate constant (Keo) for plasma to effect compartment equilibration remains unknown for clonidine, but simulation demonstrates that there will be delayed onset and offset of sedative effect after nasal administration compared with oral administration. The choice of administration route will depend on the clinical scenario; the nasal route might not always be preferable. Although the route is often chosen solely for the ease of administration, the bioavailability and kinetics must also be borne in mind because these all impact on dose, time of onset and time of offset in ways that might not be immediately obvious. Conflict of interest No conflicts of interest declared. Lee Blackburn1, Nicole Almenrader2, Peter Larsson3 & Brian J. Anderson1 1 Department of Anaesthesiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand 2 Department of Anaesthesia and Intensive Care, Policlinico Umberto I, Rome, Italy 3 Department of Physiology and Pharmacology, Section of Anaesthesiology & Intensive Care, Karolinska Institutet, Stockholm, Sweden Email: [email protected] doi:10.1111/pan.12297
341
Correspondence
References 1 Almenrader N, Larsson P, Passariello M et al. Absorption pharmacokinetics of clonidine nasal drops in children. Pediatr Anesth 2009; 19: 257– 261. 2 Larsson P, Nordlinder A, Bergendahl HT et al. Oral bioavailability of clonidine in children. Pediatr Anesth 2011; 21: 335–340.
3 Potts AL, Larsson P, Eksborg S et al. Clonidine disposition in children; a population analysis. Pediatr Anesth 2007; 17: 924–933. 4 Lonnqvist PA, Bergendahl H. Pharmacokinetics and haemodynamic response after an intravenous bolus injection of clonidine in children. Paediatr Anaesth 1993; 3: 359–364.
5 Bergendahl HT, Eksborg S, Lonnqvist PA. Low-dose intravenous clonidine in children: plasma concentrations and haemodynamic response. Acta Anaesthesiol Scand 1997; 41: 381–384.
Supraclavicular subclavian vein catheterization is still forgotten
SIR—We read the excellent article, A review of 5434 percutaneous pediatric central venous catheters inserted by anesthesiologists, by Malbezin et al. (1) with interest. Concerning the high number of patient, we are surprised that the supraclavicular subclavian vein (SSV) approach for central venous catheterization (CVC) was not used by authors (specifically trained pediatric anesthesiologist for CVC) in any of the pediatric patients. The use of SSV approach for central venous cannulation is gradually increasing in both adult and pediatric patients (2–4). It is known that SSV approach for CVC is successfully used by pediatric anesthesiologists in pediatric patients in author’s country (2). Why the authors did not choose SSV approach for CVC in any pediatric patient? Yoffa (5) described a SSV approach of CVC, advocating it as a safe method with low rate of complication in 1965. Patrick et al. (6) mentioned that SSV approach for CVC is “the forgotten central line” in 1999. Cunningham and Gallmeier (7) mentioned that “supraclavicular approach for central venous cannulation is safer, simpler, speedier method”. We think that the SSV approach is rather safe and may be considered as the first choice of CVC method whenever a central venous route is required. We have been using SSV approach as the primary alternative for CVC in both adult and pediatric patient groups. The vast majority of the inserted central venous lines by Malbezin et al. (1) were tunnelled. The use of SSV approach has no disadvantages for tunnelled types of central venous lines. Rhondali et al. (2) used the SSV approach for CVC with or without tunnelled catheters in infants and stated that the tunnelization was much easier in subclavian vein than internal jugular vein. Simi-
342
larly, Guilbert et al. (4) also mentioned that the subclavian vein is easily accessed for tunnelization in infants in their study which revealed successful results with SSV approach. Rhondali et al. (2) consider the subclavian vein as a more favorable site for long-term CVC with a supraclavicular approach in pediatric patients to avoid compression of the central venous catheter between the first rib and clavicle. We have previously reported that the use of SSV approach for CVC has lower risk of catheter compression when compared with the infraclavicular approach of subclavian vein even after sternal retraction (3). The overall complication rate of jugular venous catheterization (JVC) was reported as 1.3% and regarded as favorable when compared with the literature by the author (1). Although very rare, it is a wellknown fact that the serious neurologic damage and death subsequent to cerebral infarct due to in advertent carotid artery puncture is a major complication of JVC. The use of SSV approach for CVC avoids this serious complication. Moreover, Guilbert et al. (4) mentioned that SSV approach for central venous cannulation is “safe, reliable, with few early complications” in pediatric patients. We think that the SSV approach for CVC is a safe and preferable method in pediatric patients due to their additional advantages including the ease of neck movement, medical dressing, and catheter care by medical staff in long-term catheter usage and an improved patient comfort. We have emphasized that using the SSV approach is a safe alternative for CVC in pediatric patients; therefore, we think that the SSV approach should not be forgotten for central venous cannulation.
© 2014 John Wiley & Sons Ltd Pediatric Anesthesia 24 (2014) 339–357
