Dunk-Craaijo, J.H. (Joke H.)

Hoog, M. (Matthijs) de

Koch, B.C.P. (Birgit)

Vet, N.J. (Nienke)

Wildt, S.N. (Saskia) de

Winter, B.C.M. (Brenda) de

English

Winter, B.C. de

Hoog, M. de

Vet, N.J.

Dunk-Craaijo, J.H.

Koch, B.C.

Wildt, S.N. de

NARCIS 

Finger-Prick Blood Sampling for Therapeutic Drug Monitoring: Be Aware of Skin Contamination by Nebulized Drugs

Crossref

de Winter, Brenda

de Hoog, Matthijs

Vet, Nienke

Dunk - Craaijo, Joke

Koch, Birgit

de Wildt, Saskia

EUR Research Repository

Downloadedfromhttps://journals.lww.com/drug-monitoringbyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mRgP8KMOyN+AkRkv3XRGvHVH/xHMH4VXRsnl5rweOqM=on07/10/2020Downloadedfromhttps://journals.lww.com/drug-monitoringbyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mRgP8KMOyN+AkRkv3XRGvHVH/xHMH4VXRsnl5rweOqM=on07/10/2020LETTER TO THE EDITORFinger-Prick BloodSampling forTherapeutic DrugMonitoring: Be Awareof Skin Contaminationby Nebulized DrugsTo the Editor:Over the past few years, the num-ber of drugs for inhalation therapy andnebulizer devices has rapidly expanded.1Systemic exposure of inhalational drugsis not only estimated during drug devel-opment, but also used to monitor the ef-fects of drug therapy, including toxicity.New liquid chromatography–mass spec-trometry techniques have facilitatedtherapeutic drug monitoring using mini-mal blood volumes and dried blood spotmethods taken by finger-prick sampling.We recently performed a pharmaco-kinetic study in children receiving intra-venously administered salbutamol forsevere acute asthma.2 During data analy-sis, we noticed 8 aberrantly high concen-trations of salbutamol (Fig. 1) that couldnot be attributed to the pharmacokineticprofile of the drug, drug administrationerrors, samples taken from the drugadministration line, clinical symptoms,sample mix-ups, or other logistic errors.All children were switched back to salbu-tamol nebulization when the intravenousadministration was sufficiently reduced orstopped. An alternative explanation wascontamination of the finger-prick sampledue to drug transfer from the skin to theblood sample in the microtainer.Salbutamol may be present on the fingersas a consequence of holding the nebuliz-ing device and the subsequent touching ofthe mouth or the inner side of the deviceduring therapy. This contamination mayresult in the overestimation of the trueblood concentration.3 Totally, 9 samples(7%) were obtained through a finger prickafter switching back to nebulization, and 6of these samples were found to haveaberrantly high drug concentrations.Samples during nebulization before thestart of intravenous therapy were all takenfrom an arterial line or central venouscatheter, instead of using a finger prick.As our pharmacy department per-forms regular therapeutic drug monitor-ing for inhalational drugs, potential drugcontamination of the skin may seriouslyimpact interpretation of results andpatient care, for other drugs also. Wetherefore designed a quality improvementproject that tested the hypothesis thatnebulized drugs may contaminate a pa-tient’s fingers, leading to false high bloodconcentrations from finger-prick samples.The medical ethical review board granteda waiver after reviewing the protocol. Inaddition, the healthy volunteers providedwritten informed consent.METHODSWe performed 2 experiments: thefirst was to examine proof-of-concept,and the second was to investigate theeffects of mask holding and 2 cleaningmethods.For the first experiment, a researchnurse prepared the salbutamol nebuliza-tion equipment in accordance with theprotocol used in clinical care: 2-mLNaCl 0.9% and 2-mL salbutamol 2 mg/mL were combined in the ICU nebuliz-ing system (Hudson ACI, Paediatricaerosol mask combined with HudsonMicro-Mist nebulizer). The researchnurse turned on the airflow. The pre-pared salbutamol solution was nebulizedonto the hand of a salbutamol-free adultvolunteer. The hand was placed directlyat the opening of the nebulizing mask.This volunteer was not involved in thepreparation of the nebulizer set-up anddid not touch the salbutamol solution.After approximately 5 minutes, a finger-prick sample of approximately 0.5 mLwas taken from the sprayed hand intoa microtainer.The second experiment was per-formed in 2 healthy adult volunteers.The first volunteer held the nebulizer intheir left hand at the bottom, close to thesalbutamol reservoir, in the same man-ner as older children. The second vol-unteer held the nebulizer with their lefthand at the mask, in the same manner asyounger children. Both volunteerssprayed the salbutamol from a distanceof 10 cm onto their right hand overa period of 5 minutes. On their righthand, one finger was not cleaned, onefinger was swabbed with alcohol tomimic standard disinfection beforeblood sampling, and one finger wasthoroughly cleaned with water and soap.A finger-prick blood sample was takenfrom each of these 3 fingers in addition toone finger-prick sample from the left handholding the mask. All plasma sampleswere stored at 280°C until analysis usinga validated liquid chromatography–massspectrometry method.RESULTSIn the first experiment, sprayingsalbutamol over the hand of the volun-teer resulted in concentrations of .1000mcg/L R-salbutamol and .1000 mcg/LS-salbutamol. This was much higherthan the range of concentrations ana-lyzed during intravenous salbutamolinfusion in children included in the trial(R-salbutamol: median, 66 mcg/L;S-salbutamol: median, 106 mcg/L), butwithin the range of concentrations foundin the 8 outlier samples in the pilot study(R-salbutamol range: 504–1918 mcg/L;S-salbutamol range: 636–2018 mcg/L).In the second experiment, the con-centrations measured on the uncleanedfinger were 686 and 639 mcg/L, respec-tively, for one volunteer, and 82 and75 mcg/L for the other volunteer, respec-tively, for R-salbutamol and S-salbutamol.Cleaning with alcohol wipes resulted in39%–56% lower salbutamol concentra-tions for both volunteers (398 and 36mcg/L R-salbutamol, 389 and 34 mcg/LS-salbutamol). Cleaning with waterand soap decreased the concentrationsby 94%–100% (30 and 5 mcg/LR-salbutamol, respectively; 29 mcg/Land ,2 mcg/L S-salbutamol, respec-tively). The concentrations measuredon the finger of the left hand were 8mcg/L for R-salbutamol and 10 mcg/Lfor S-salbutamol for the volunteer hold-ing the system at the reservoir and 78mcg/L for R-salbutamol and 56 mcg/LThe authors declare no conflict of interest.512 Ther Drug Monit  Volume 42, Number 3, June 2020Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.for S-salbutamol for the volunteer hold-ing the system at the mask.CONCLUSIONSAfter nebulizing, skin contami-nation can result in falsely elevatedplasma concentrations in finger-prickblood samples. The contamination isprobably lesser on the hand holding thesystem at the reservoir than the mask;however, the fingers are still contami-nated. The extreme high concentrationsmay be the result of a longer nebulizingperiod, or the child touching themouth or the inner side of the device.We expect this contamination iscomparable in new dried-blood spottechniques using finger-prick sam-pling. Finger-prick blood samplingshould be used cautiously in therapeu-tic drug monitoring and pharmacoki-netic studies of nebulized drugs. Toovercome this problem, blood sam-pling practices for these drugs shouldbe carefully considered to preventelevated levels and correspondingbiased conclusions. As a precaution,wearing gloves on the sampling handor traditional venipuncture (if the sam-pling place is covered during inhala-tion) should be considered. Cleaningtechniques using both alcohol wipes orwater and soap result in unpredictablecontamination.Brenda C. M. de Winter, PhD*Matthijs de Hoog, MD†Nienke J. Vet, PhD†Joke H. Dunk-Craaijo†Birgit C. P. Koch, PhD*Saskia N. de Wildt, MD, PhD†,‡*Department of Hospital Pharmacy,Erasmus University Medical Center,Rotterdam, the Netherlands†Intensive Care and Department ofPediatric Surgery,Erasmus MC-Sophia Children’s Hospital,Rotterdam, the Netherlands‡Department ofPharmacology and Toxicology,Radboud University,Nijmegen, the NetherlandsREFERENCES1. Martin AR, Finlay WH. Nebulizers for drugdelivery to the lungs. Expert Opin Drug Deliv.2015;12:889–900.2. Vet N, de Winter BCM, de Wildt SN, et al.Population pharmacokinetics of intravenoussalbutamol in children with refractory statusasthmaticus. Clin Pharmacokinet. 2019;59:257–264.3. Redmann S, Wainwright C, Stacey S, et al.Misleading high tobramycin plasma concentra-tions can be caused by skin contamination offingerprick blood following inhalation of nebu-lized tobramycin (TOBI): a short report. TherDrug Monit. 2005;27:205–207.FIGURE 1. Concentration–time profiles, including infusion rate for 2 patients inwhich aberrantly high concentrations of salbutamol, were analyzed. The measured R-salbutamol and S-salbutamol concentrations and infusion rates are presented in thefigure. Patient A restarted nebulization at 10 hours after inclusion, and patient B re-started nebulization at 18 hours after inclusion.Ther Drug Monit  Volume 42, Number 3, June 2020 Letter to the EditorCopyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. 513Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

Erasmus University Digital Repository

Downloadedfromhttps://journals.lww.com/drug-monitoringbyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mRgP8KMOyN+AkRkv3XRGvHVH/xHMH4VXRsnl5rweOqM=on06/03/2020Downloadedfromhttps://journals.lww.com/drug-monitoringbyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mRgP8KMOyN+AkRkv3XRGvHVH/xHMH4VXRsnl5rweOqM=on06/03/2020LETTER TO THE EDITORFinger-Prick BloodSampling forTherapeutic DrugMonitoring: Be Awareof Skin Contaminationby Nebulized DrugsTo the Editor:Over the past few years, the num-ber of drugs for inhalation therapy andnebulizer devices has rapidly expanded.1Systemic exposure of inhalational drugsis not only estimated during drug devel-opment, but also used to monitor the ef-fects of drug therapy, including toxicity.New liquid chromatography–mass spec-trometry techniques have facilitatedtherapeutic drug monitoring using mini-mal blood volumes and dried blood spotmethods taken by finger-prick sampling.We recently performed a pharmaco-kinetic study in children receiving intra-venously administered salbutamol forsevere acute asthma.2 During data analy-sis, we noticed 8 aberrantly high concen-trations of salbutamol (Fig. 1) that couldnot be attributed to the pharmacokineticprofile of the drug, drug administrationerrors, samples taken from the drugadministration line, clinical symptoms,sample mix-ups, or other logistic errors.All children were switched back to salbu-tamol nebulization when the intravenousadministration was sufficiently reduced orstopped. An alternative explanation wascontamination of the finger-prick sampledue to drug transfer from the skin to theblood sample in the microtainer.Salbutamol may be present on the fingersas a consequence of holding the nebuliz-ing device and the subsequent touching ofthe mouth or the inner side of the deviceduring therapy. This contamination mayresult in the overestimation of the trueblood concentration.3 Totally, 9 samples(7%) were obtained through a finger prickafter switching back to nebulization, and 6of these samples were found to haveaberrantly high drug concentrations.Samples during nebulization before thestart of intravenous therapy were all takenfrom an arterial line or central venouscatheter, instead of using a finger prick.As our pharmacy department per-forms regular therapeutic drug monitor-ing for inhalational drugs, potential drugcontamination of the skin may seriouslyimpact interpretation of results andpatient care, for other drugs also. Wetherefore designed a quality improvementproject that tested the hypothesis thatnebulized drugs may contaminate a pa-tient’s fingers, leading to false high bloodconcentrations from finger-prick samples.The medical ethical review board granteda waiver after reviewing the protocol. Inaddition, the healthy volunteers providedwritten informed consent.METHODSWe performed 2 experiments: thefirst was to examine proof-of-concept,and the second was to investigate theeffects of mask holding and 2 cleaningmethods.For the first experiment, a researchnurse prepared the salbutamol nebuliza-tion equipment in accordance with theprotocol used in clinical care: 2-mLNaCl 0.9% and 2-mL salbutamol 2 mg/mL were combined in the ICU nebuliz-ing system (Hudson ACI, Paediatricaerosol mask combined with HudsonMicro-Mist nebulizer). The researchnurse turned on the airflow. The pre-pared salbutamol solution was nebulizedonto the hand of a salbutamol-free adultvolunteer. The hand was placed directlyat the opening of the nebulizing mask.This volunteer was not involved in thepreparation of the nebulizer set-up anddid not touch the salbutamol solution.After approximately 5 minutes, a finger-prick sample of approximately 0.5 mLwas taken from the sprayed hand intoa microtainer.The second experiment was per-formed in 2 healthy adult volunteers.The first volunteer held the nebulizer intheir left hand at the bottom, close to thesalbutamol reservoir, in the same man-ner as older children. The second vol-unteer held the nebulizer with their lefthand at the mask, in the same manner asyounger children. Both volunteerssprayed the salbutamol from a distanceof 10 cm onto their right hand overa period of 5 minutes. On their righthand, one finger was not cleaned, onefinger was swabbed with alcohol tomimic standard disinfection beforeblood sampling, and one finger wasthoroughly cleaned with water and soap.A finger-prick blood sample was takenfrom each of these 3 fingers in addition toone finger-prick sample from the left handholding the mask. All plasma sampleswere stored at 280°C until analysis usinga validated liquid chromatography–massspectrometry method.RESULTSIn the first experiment, sprayingsalbutamol over the hand of the volun-teer resulted in concentrations of .1000mcg/L R-salbutamol and .1000 mcg/LS-salbutamol. This was much higherthan the range of concentrations ana-lyzed during intravenous salbutamolinfusion in children included in the trial(R-salbutamol: median, 66 mcg/L;S-salbutamol: median, 106 mcg/L), butwithin the range of concentrations foundin the 8 outlier samples in the pilot study(R-salbutamol range: 504–1918 mcg/L;S-salbutamol range: 636–2018 mcg/L).In the second experiment, the con-centrations measured on the uncleanedfinger were 686 and 639 mcg/L, respec-tively, for one volunteer, and 82 and75 mcg/L for the other volunteer, respec-tively, for R-salbutamol and S-salbutamol.Cleaning with alcohol wipes resulted in39%–56% lower salbutamol concentra-tions for both volunteers (398 and 36mcg/L R-salbutamol, 389 and 34 mcg/LS-salbutamol). Cleaning with waterand soap decreased the concentrationsby 94%–100% (30 and 5 mcg/LR-salbutamol, respectively; 29 mcg/Land ,2 mcg/L S-salbutamol, respec-tively). The concentrations measuredon the finger of the left hand were 8mcg/L for R-salbutamol and 10 mcg/Lfor S-salbutamol for the volunteer hold-ing the system at the reservoir and 78mcg/L for R-salbutamol and 56 mcg/LThe authors declare no conflict of interest.512 Ther Drug Monit  Volume 42, Number 3, June 2020Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.for S-salbutamol for the volunteer hold-ing the system at the mask.CONCLUSIONSAfter nebulizing, skin contami-nation can result in falsely elevatedplasma concentrations in finger-prickblood samples. The contamination isprobably lesser on the hand holding thesystem at the reservoir than the mask;however, the fingers are still contami-nated. The extreme high concentrationsmay be the result of a longer nebulizingperiod, or the child touching themouth or the inner side of the device.We expect this contamination iscomparable in new dried-blood spottechniques using finger-prick sam-pling. Finger-prick blood samplingshould be used cautiously in therapeu-tic drug monitoring and pharmacoki-netic studies of nebulized drugs. Toovercome this problem, blood sam-pling practices for these drugs shouldbe carefully considered to preventelevated levels and correspondingbiased conclusions. As a precaution,wearing gloves on the sampling handor traditional venipuncture (if the sam-pling place is covered during inhala-tion) should be considered. Cleaningtechniques using both alcohol wipes orwater and soap result in unpredictablecontamination.Brenda C. M. de Winter, PhD*Matthijs de Hoog, MD†Nienke J. Vet, PhD†Joke H. Dunk-Craaijo†Birgit C. P. Koch, PhD*Saskia N. de Wildt, MD, PhD†,‡*Department of Hospital Pharmacy,Erasmus University Medical Center,Rotterdam, the Netherlands†Intensive Care and Department ofPediatric Surgery,Erasmus MC-Sophia Children’s Hospital,Rotterdam, the Netherlands‡Department ofPharmacology and Toxicology,Radboud University,Nijmegen, the NetherlandsREFERENCES1. Martin AR, Finlay WH. Nebulizers for drugdelivery to the lungs. Expert Opin Drug Deliv.2015;12:889–900.2. Vet N, de Winter BCM, de Wildt SN, et al.Population pharmacokinetics of intravenoussalbutamol in children with refractory statusasthmaticus. Clin Pharmacokinet. 2019;59:257–264.3. Redmann S, Wainwright C, Stacey S, et al.Misleading high tobramycin plasma concentra-tions can be caused by skin contamination offingerprick blood following inhalation of nebu-lized tobramycin (TOBI): a short report. TherDrug Monit. 2005;27:205–207.FIGURE 1. Concentration–time profiles, including infusion rate for 2 patients inwhich aberrantly high concentrations of salbutamol, were analyzed. The measured R-salbutamol and S-salbutamol concentrations and infusion rates are presented in thefigure. Patient A restarted nebulization at 10 hours after inclusion, and patient B re-started nebulization at 18 hours after inclusion.Ther Drug Monit  Volume 42, Number 3, June 2020 Letter to the EditorCopyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. 513Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

de Hoog, M.

Koch, B.C.P.

EUR Research Information PortalFinger-Prick Blood Sampling for Therapeutic Drug Monitoring: Be Aware of SkinContamination by Nebulized DrugsPublished in:Therapeutic Drug MonitoringPublication status and date:Published: 01/01/2020DOI (link to publisher):10.1097/ftd.0000000000000746Document VersionPublisher's PDF, also known as Version of recordCitation for the published version (APA):de Winter, B., de Hoog, M., Vet, N., Dunk - Craaijo, J., Koch, B., & de Wildt, S. (2020). Finger-Prick Blood Sampling forTherapeutic Drug Monitoring: Be Aware of Skin Contamination by Nebulized Drugs. Therapeutic Drug Monitoring, 42(3), 512-513. https://doi.org/10.1097/ftd.0000000000000746Link to publication on the EUR Research Information PortalTerms and Conditions of UseExcept as permitted by the applicable copyright law, you may not reproduce or make this material available to any third partywithout the prior written permission from the copyright holder(s). Copyright law allows the following uses of this materialwithout prior permission:            • you may download, save and print a copy of this material for your personal use only;            • you may share the EUR portal link to this material.In case the material is published with an open access license (e.g. a Creative Commons (CC) license), other uses may beallowed. Please check the terms and conditions of the specific license.Take-down policyIf you believe that this material infringes your copyright and/or any other intellectual property rights, you may request itsremoval by contacting us at the following email address: openaccess.library@eur.nl. Please provide us with all the relevantinformation, including the reasons why you believe any of your rights have been infringed. In case of a legitimate complaint,we will make the material inaccessible and/or remove it from the website.Downloadedfromhttps://journals.lww.com/drug-monitoringbyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mRgP8KMOyN+AkRkv3XRGvHVH/xHMH4VXRsnl5rweOqM=on07/10/2020Downloadedfromhttps://journals.lww.com/drug-monitoringbyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mRgP8KMOyN+AkRkv3XRGvHVH/xHMH4VXRsnl5rweOqM=on07/10/2020LETTER TO THE EDITORFinger-Prick BloodSampling forTherapeutic DrugMonitoring: Be Awareof Skin Contaminationby Nebulized DrugsTo the Editor:Over the past few years, the num-ber of drugs for inhalation therapy andnebulizer devices has rapidly expanded.1Systemic exposure of inhalational drugsis not only estimated during drug devel-opment, but also used to monitor the ef-fects of drug therapy, including toxicity.New liquid chromatography–mass spec-trometry techniques have facilitatedtherapeutic drug monitoring using mini-mal blood volumes and dried blood spotmethods taken by finger-prick sampling.We recently performed a pharmaco-kinetic study in children receiving intra-venously administered salbutamol forsevere acute asthma.2 During data analy-sis, we noticed 8 aberrantly high concen-trations of salbutamol (Fig. 1) that couldnot be attributed to the pharmacokineticprofile of the drug, drug administrationerrors, samples taken from the drugadministration line, clinical symptoms,sample mix-ups, or other logistic errors.All children were switched back to salbu-tamol nebulization when the intravenousadministration was sufficiently reduced orstopped. An alternative explanation wascontamination of the finger-prick sampledue to drug transfer from the skin to theblood sample in the microtainer.Salbutamol may be present on the fingersas a consequence of holding the nebuliz-ing device and the subsequent touching ofthe mouth or the inner side of the deviceduring therapy. This contamination mayresult in the overestimation of the trueblood concentration.3 Totally, 9 samples(7%) were obtained through a finger prickafter switching back to nebulization, and 6of these samples were found to haveaberrantly high drug concentrations.Samples during nebulization before thestart of intravenous therapy were all takenfrom an arterial line or central venouscatheter, instead of using a finger prick.As our pharmacy department per-forms regular therapeutic drug monitor-ing for inhalational drugs, potential drugcontamination of the skin may seriouslyimpact interpretation of results andpatient care, for other drugs also. Wetherefore designed a quality improvementproject that tested the hypothesis thatnebulized drugs may contaminate a pa-tient’s fingers, leading to false high bloodconcentrations from finger-prick samples.The medical ethical review board granteda waiver after reviewing the protocol. Inaddition, the healthy volunteers providedwritten informed consent.METHODSWe performed 2 experiments: thefirst was to examine proof-of-concept,and the second was to investigate theeffects of mask holding and 2 cleaningmethods.For the first experiment, a researchnurse prepared the salbutamol nebuliza-tion equipment in accordance with theprotocol used in clinical care: 2-mLNaCl 0.9% and 2-mL salbutamol 2 mg/mL were combined in the ICU nebuliz-ing system (Hudson ACI, Paediatricaerosol mask combined with HudsonMicro-Mist nebulizer). The researchnurse turned on the airflow. The pre-pared salbutamol solution was nebulizedonto the hand of a salbutamol-free adultvolunteer. The hand was placed directlyat the opening of the nebulizing mask.This volunteer was not involved in thepreparation of the nebulizer set-up anddid not touch the salbutamol solution.After approximately 5 minutes, a finger-prick sample of approximately 0.5 mLwas taken from the sprayed hand intoa microtainer.The second experiment was per-formed in 2 healthy adult volunteers.The first volunteer held the nebulizer intheir left hand at the bottom, close to thesalbutamol reservoir, in the same man-ner as older children. The second vol-unteer held the nebulizer with their lefthand at the mask, in the same manner asyounger children. Both volunteerssprayed the salbutamol from a distanceof 10 cm onto their right hand overa period of 5 minutes. On their righthand, one finger was not cleaned, onefinger was swabbed with alcohol tomimic standard disinfection beforeblood sampling, and one finger wasthoroughly cleaned with water and soap.A finger-prick blood sample was takenfrom each of these 3 fingers in addition toone finger-prick sample from the left handholding the mask. All plasma sampleswere stored at 280°C until analysis usinga validated liquid chromatography–massspectrometry method.RESULTSIn the first experiment, sprayingsalbutamol over the hand of the volun-teer resulted in concentrations of .1000mcg/L R-salbutamol and .1000 mcg/LS-salbutamol. This was much higherthan the range of concentrations ana-lyzed during intravenous salbutamolinfusion in children included in the trial(R-salbutamol: median, 66 mcg/L;S-salbutamol: median, 106 mcg/L), butwithin the range of concentrations foundin the 8 outlier samples in the pilot study(R-salbutamol range: 504–1918 mcg/L;S-salbutamol range: 636–2018 mcg/L).In the second experiment, the con-centrations measured on the uncleanedfinger were 686 and 639 mcg/L, respec-tively, for one volunteer, and 82 and75 mcg/L for the other volunteer, respec-tively, for R-salbutamol and S-salbutamol.Cleaning with alcohol wipes resulted in39%–56% lower salbutamol concentra-tions for both volunteers (398 and 36mcg/L R-salbutamol, 389 and 34 mcg/LS-salbutamol). Cleaning with waterand soap decreased the concentrationsby 94%–100% (30 and 5 mcg/LR-salbutamol, respectively; 29 mcg/Land ,2 mcg/L S-salbutamol, respec-tively). The concentrations measuredon the finger of the left hand were 8mcg/L for R-salbutamol and 10 mcg/Lfor S-salbutamol for the volunteer hold-ing the system at the reservoir and 78mcg/L for R-salbutamol and 56 mcg/LThe authors declare no conflict of interest.512 Ther Drug Monit  Volume 42, Number 3, June 2020Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.for S-salbutamol for the volunteer hold-ing the system at the mask.CONCLUSIONSAfter nebulizing, skin contami-nation can result in falsely elevatedplasma concentrations in finger-prickblood samples. The contamination isprobably lesser on the hand holding thesystem at the reservoir than the mask;however, the fingers are still contami-nated. The extreme high concentrationsmay be the result of a longer nebulizingperiod, or the child touching themouth or the inner side of the device.We expect this contamination iscomparable in new dried-blood spottechniques using finger-prick sam-pling. Finger-prick blood samplingshould be used cautiously in therapeu-tic drug monitoring and pharmacoki-netic studies of nebulized drugs. Toovercome this problem, blood sam-pling practices for these drugs shouldbe carefully considered to preventelevated levels and correspondingbiased conclusions. As a precaution,wearing gloves on the sampling handor traditional venipuncture (if the sam-pling place is covered during inhala-tion) should be considered. Cleaningtechniques using both alcohol wipes orwater and soap result in unpredictablecontamination.Brenda C. M. de Winter, PhD*Matthijs de Hoog, MD†Nienke J. Vet, PhD†Joke H. Dunk-Craaijo†Birgit C. P. Koch, PhD*Saskia N. de Wildt, MD, PhD†,‡*Department of Hospital Pharmacy,Erasmus University Medical Center,Rotterdam, the Netherlands†Intensive Care and Department ofPediatric Surgery,Erasmus MC-Sophia Children’s Hospital,Rotterdam, the Netherlands‡Department ofPharmacology and Toxicology,Radboud University,Nijmegen, the NetherlandsREFERENCES1. Martin AR, Finlay WH. Nebulizers for drugdelivery to the lungs. Expert Opin Drug Deliv.2015;12:889–900.2. Vet N, de Winter BCM, de Wildt SN, et al.Population pharmacokinetics of intravenoussalbutamol in children with refractory statusasthmaticus. Clin Pharmacokinet. 2019;59:257–264.3. Redmann S, Wainwright C, Stacey S, et al.Misleading high tobramycin plasma concentra-tions can be caused by skin contamination offingerprick blood following inhalation of nebu-lized tobramycin (TOBI): a short report. TherDrug Monit. 2005;27:205–207.FIGURE 1. Concentration–time profiles, including infusion rate for 2 patients inwhich aberrantly high concentrations of salbutamol, were analyzed. The measured R-salbutamol and S-salbutamol concentrations and infusion rates are presented in thefigure. Patient A restarted nebulization at 10 hours after inclusion, and patient B re-started nebulization at 18 hours after inclusion.Ther Drug Monit  Volume 42, Number 3, June 2020 Letter to the EditorCopyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. 513Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

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Finger-Prick Blood Sampling for Therapeutic Drug Monitoring: Be Aware of Skin Contamination by Nebulized Drugs

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