Scientific Letter
Use of topical nitroglycerin in newborns with ischaemic injuries after vascular cannulation
Uso de nitroglicerina tópica en neonatos con lesiones isquémicas tras canalización de vasos
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class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Prado" "apellidos" => "Sánchez Ruiz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Mercedes" "apellidos" => "Ludeña del Río" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Jesús Cecilio" "apellidos" => "López-Menchero Oliva" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Miguel Ángel" "apellidos" => "García Cabezas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Unidad de Neonatología, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio Pediatría, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Uso de nitroglicerina tópica en neonatos con lesiones isquémicas tras canalización de vasos" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 706 "Ancho" => 950 "Tamanyo" => 88657 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Example of vasospasm and ischaemic lesions in the hand of a newborn following peripheral cannulation.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Vascular cannulation in the neonatal intensive care unit (UCIN) can cause severe ischaemic complications. In some instances, conservative management of these complications is unsuccessful and they may require pharmacological treatment. We describe a series of four clinical cases with favourable outcomes following use of topical nitroglycerin.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the cases of four patients admitted to the NICU, two of them born preterm at 24<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>6 and 35 weeks, respectively, and two born at term. The extremely preterm newborn underwent cannulation of the umbilical vein and artery, after which he developed pallor in his left leg and eventually necrosis in three toes. The other three patients developed ischaemic lesions in the fingers after placement of percutaneously inserted central catheters and peripheral venous catheters in the upper extremities (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). All of them were managed conservatively and their catheters removed. Since there was no improvement, topical treatment with 2% nitroglycerin cream was prescribed (dose of 4<span class="elsevierStyleHsp" style=""></span>mm/kg), which was maintained for 5–18 days, to which all patients responded favourably (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). None of the patients experienced adverse effects from the treatment.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Placement of central and peripheral catheters is a common procedure in the NICU. This technique can lead to ischaemic complications, which develope more frequently in patients in critical condition or born preterm. The reason is that their blood vessels are more susceptible to rupturing, vasospasm and thrombosis, which increases the risk of ischaemia and necrosis in adjacent tissues.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The initial treatment of this complication includes removal of the catheter and application of heat to the contralateral region to promote vasodilation. Occasionally, these measures are insufficient and patients require pharmacological treatment. Research has shown that anticoagulants, thrombolytics or local infiltration of phentolamine or hyaluronidase offer limited benefits and cause side effects when administered systemically.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Nitroglycerin is a nitric oxide donor that has a direct effect as a smooth muscle relaxant, leading to vasodilation of arteries and veins, and consequently improving blood flow after vasospasm or ischaemia.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> Historically, it has been used for the treatment of Raynoud's phenomenon or purpura fulminans. Its use in adults is approved for the treatment of angina, myocardial infarction and arterial hypertension. In the paediatric age group, it has been used off-label to treat chronic anal fissure. In recent years, evidence has been published on the efficacy of nitroglycerin to treat ischaemic complications associated to vascular cannulation or drug extravasation.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In the cases presented here, nitroglycerin was used as an adjuvant to physical measures. Samiee-Zafarghandy and Mosalli have published several case series and reported similar outcomes with no associated adverse effects, consistent with what we observed in our patients.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Studies in the literature have reported the use of a variety of doses ranging between 0.12<span class="elsevierStyleHsp" style=""></span>mg/kg and 2.5<span class="elsevierStyleHsp" style=""></span>mg/kg. Recent publications have established a dose of 1.22<span class="elsevierStyleHsp" style=""></span>mg/kg (4<span class="elsevierStyleHsp" style=""></span>mm/kg) as safe and efficacious in patients that do not respond to conservative measures. This is the dosage that has been applied in our hospital.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> The topical 2% nitroglycerin formulation was compounded at the hospital pharmacy following current recommendations.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The time to initiate treatment has not been well defined in the literature. In our patients, nitroglycerin was applied in the early hours following the development of ischaemia, but other authors have reported good outcomes with later treatment. The duration of treatment was determined based on the patient's response, and ranged between five and eighteen days, which is consistent with the durations reported in the literature.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Due to the scarcity of studies and the lack of consensus on the safety and dosage of topical nitroglycerin in children, the use of this drug has been limited for fear of side effects, especially in preterm newborns, who have immature skin and a limited autoregulation of blood flow and therefore are at increased risk of brain haemorrhage. The adverse effects reported most frequently are headache, dizziness, hypotension and methaemoglobinaemia. In our case series, we monitored blood pressure hourly and methaemoglobin daily, and performed a transfontanellar ultrasound before and after treatment with nitroglycerin, and did not observe any significant adverse effects.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Although the available data on the use of nitroglycerin is limited to the description of case series, the outcomes are promising. Few clinical trials have been conducted to assess the use of nitroglycerin in newborns, and we want to emphasise the need to carry out prospective studies with larger samples. Only then will it be possible to standardise prescription regimens for the treatment of arterial vasospasm following vascular cannulation.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Vivar del Hoyo P, Sánchez Ruiz P, Ludeña del Río M, López-Menchero Oliva JC, García Cabezas MA. Uso de nitroglicerina tópica en neonatos con lesiones isquémicas tras canalización de vasos tropical. An Pediatr (Barc). 2016;85:155–156.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 706 "Ancho" => 950 "Tamanyo" => 88657 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Example of vasospasm and ischaemic lesions in the hand of a newborn following peripheral cannulation.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 711 "Ancho" => 1600 "Tamanyo" => 125155 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Outcome of ischaemic lesions in the toes of a preterm infant after topical treatment with 2% nitroglycerin.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Topical nitroglycerin in neonates with tissue injury: a case report and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S. 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Paes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2013/608516" "Revista" => array:5 [ "tituloSerie" => "Case Rep Pediatr" "fecha" => "2013" "volumen" => "2013" "paginaInicial" => "608516" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24251058" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nitroglycerin for severe ischaemic injury after peripheral arterial line in a preterm infant" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R. Kamar" 1 => "J.J. van Vonderen" 2 => "E. Lopriore" 3 => "A.B. Te Pas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/apa.12141" "Revista" => array:6 [ "tituloSerie" => "Acta Paediatr" "fecha" => "2013" "volumen" => "102" "paginaInicial" => "e144" "paginaFinal" => "e145" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23301717" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Resolution of peripheral tissue ischemia secondary to arterial vasospasm following treatment with a topical nitroglycerin device in two newborns: case reports" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Maffei" 1 => "M. Rinaldi" 2 => "G. Rinaldi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1515/JPM.2006.047" "Revista" => array:5 [ "tituloSerie" => "J Perinat Med" "fecha" => "2006" "volumen" => "34" "paginaInicial" => "252" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16602850" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23412879/0000008500000003/v1_201608250218/S2341287916300758/v1_201608250218/en/main.assets" "Apartado" => array:4 [ "identificador" => "38181" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23412879/0000008500000003/v1_201608250218/S2341287916300758/v1_201608250218/en/main.pdf?idApp=UINPBA00005H&text.app=https://analesdepediatria.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287916300758?idApp=UINPBA00005H" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 16 | 6 | 22 |
| 2024 October | 112 | 56 | 168 |
| 2024 September | 137 | 37 | 174 |
| 2024 August | 206 | 72 | 278 |
| 2024 July | 174 | 43 | 217 |
| 2024 June | 140 | 30 | 170 |
| 2024 May | 128 | 49 | 177 |
| 2024 April | 101 | 28 | 129 |
| 2024 March | 145 | 24 | 169 |
| 2024 February | 121 | 31 | 152 |
| 2024 January | 98 | 28 | 126 |
| 2023 December | 113 | 23 | 136 |
| 2023 November | 145 | 32 | 177 |
| 2023 October | 120 | 36 | 156 |
| 2023 September | 111 | 31 | 142 |
| 2023 August | 111 | 22 | 133 |
| 2023 July | 93 | 28 | 121 |
| 2023 June | 106 | 35 | 141 |
| 2023 May | 119 | 27 | 146 |
| 2023 April | 114 | 21 | 135 |
| 2023 March | 123 | 27 | 150 |
| 2023 February | 135 | 27 | 162 |
| 2023 January | 128 | 23 | 151 |
| 2022 December | 141 | 24 | 165 |
| 2022 November | 122 | 37 | 159 |
| 2022 October | 106 | 42 | 148 |
| 2022 September | 120 | 36 | 156 |
| 2022 August | 110 | 56 | 166 |
| 2022 July | 113 | 29 | 142 |
| 2022 June | 128 | 45 | 173 |
| 2022 May | 156 | 48 | 204 |
| 2022 April | 107 | 39 | 146 |
| 2022 March | 146 | 44 | 190 |
| 2022 February | 129 | 52 | 181 |
| 2022 January | 141 | 40 | 181 |
| 2021 December | 114 | 53 | 167 |
| 2021 November | 127 | 59 | 186 |
| 2021 October | 149 | 66 | 215 |
| 2021 September | 116 | 54 | 170 |
| 2021 August | 112 | 65 | 177 |
| 2021 July | 111 | 53 | 164 |
| 2021 June | 156 | 65 | 221 |
| 2021 May | 142 | 59 | 201 |
| 2021 April | 360 | 98 | 458 |
| 2021 March | 181 | 45 | 226 |
| 2021 February | 139 | 34 | 173 |
| 2021 January | 174 | 36 | 210 |
| 2020 December | 138 | 45 | 183 |
| 2020 November | 97 | 40 | 137 |
| 2020 October | 120 | 20 | 140 |
| 2020 September | 150 | 24 | 174 |
| 2020 August | 172 | 28 | 200 |
| 2020 July | 131 | 25 | 156 |
| 2020 June | 133 | 23 | 156 |
| 2020 May | 108 | 26 | 134 |
| 2020 April | 170 | 32 | 202 |
| 2020 March | 86 | 26 | 112 |
| 2020 February | 97 | 19 | 116 |
| 2020 January | 89 | 31 | 120 |
| 2019 December | 111 | 31 | 142 |
| 2019 November | 81 | 18 | 99 |
| 2019 October | 78 | 9 | 87 |
| 2019 September | 100 | 16 | 116 |
| 2019 August | 85 | 37 | 122 |
| 2019 July | 81 | 26 | 107 |
| 2019 June | 81 | 26 | 107 |
| 2019 May | 164 | 50 | 214 |
| 2019 April | 147 | 37 | 184 |
| 2019 March | 72 | 28 | 100 |
| 2019 February | 70 | 30 | 100 |
| 2019 January | 88 | 25 | 113 |
| 2018 December | 70 | 37 | 107 |
| 2018 November | 91 | 40 | 131 |
| 2018 October | 119 | 44 | 163 |
| 2018 September | 73 | 29 | 102 |
| 2018 August | 4 | 0 | 4 |
| 2018 July | 1 | 0 | 1 |
| 2018 June | 3 | 0 | 3 |
| 2018 May | 21 | 0 | 21 |
| 2018 April | 49 | 0 | 49 |
| 2018 March | 41 | 0 | 41 |
| 2018 February | 47 | 0 | 47 |
| 2018 January | 34 | 0 | 34 |
| 2017 December | 25 | 0 | 25 |
| 2017 November | 47 | 0 | 47 |
| 2017 October | 26 | 0 | 26 |
| 2017 September | 21 | 0 | 21 |
| 2017 August | 14 | 0 | 14 |
| 2017 July | 39 | 2 | 41 |
| 2017 June | 20 | 9 | 29 |
| 2017 May | 36 | 15 | 51 |
| 2017 April | 32 | 9 | 41 |
| 2017 March | 16 | 6 | 22 |
| 2017 February | 45 | 10 | 55 |
| 2017 January | 11 | 2 | 13 |
| 2016 December | 24 | 12 | 36 |
| 2016 November | 29 | 17 | 46 |
| 2016 October | 33 | 22 | 55 |
| 2016 September | 77 | 29 | 106 |
| 2016 August | 27 | 4 | 31 |
| 2016 July | 5 | 6 | 11 |
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