WO2022179958A1

WO2022179958A1 - Assembly for tracheal instillation of fluid medicaments in infants supported by non-invasive ventilation

Info

Publication number: WO2022179958A1
Application number: PCT/EP2022/054166
Authority: WO
Inventors: Maurizio Radicioni
Original assignee: Maurizio Radicioni
Priority date: 2021-02-28
Filing date: 2022-02-19
Publication date: 2022-09-01
Also published as: EP4297834A1

Abstract

An assembly (1) for tracheal instillation of fluid medicaments, particularly in preterm infants supported by non-invasive ventilation, comprises a microcatheter (2), a guidewire (4) and a gripper (17). The microcatheter comprises a proximal rigid, hollow connector 8 and a distal very thin, soft composite tube (3) terminating in a coextruded rounded tip. Three color-coded circumferential bands (14), (15), (16) on the distal end of the soft composite tube guide positioning of the coextruded rounded tip within neonatal trachea under direct laryngoscopy. The slidably receptive guidewire inserted into the microcatheter stiffens the soft composite tube for introduction into the infant's airway and restores softness thereto after removal. A gripper attached to the soft composite tube improves handling as well as insertion depth control.

Description

ASSEMBLY FOR TRACHEAL INSTILLATION OF FLUID MEDICAMENTS IN INFANTS SUPPORTED BY NON-INVASIVE VENTILATION.

CROSS-REFERENCE TO RELATED APPLICATIONS. The present application claims the priority to and the benefit of U.S. Non-Provisional Utility Patent Application No.17/364,229 entitled “ASSEMBLY FOR TRACHEAL INSTILLATION OF FLUID MEDICAMENTS IN INFANTS SUPPORTED BY NON-INVASIVE VENTILATION” and filed on Jun. 30. 2021, which claims the priority to and the benefit of U.S. Provisional Application No. 63/200,299 filed Feb. 28. 2021, the full disclosures of which are incorporated herein by reference.

The invention relates to the instillation of one or more fluid medicaments into a conduit of a person supported by non-invasive ventilation while spontaneous breathing is allowed, in order to prevent, among other things, the collapsing of his/her pulmonary alveoli. More specifically, the invention relates to the instillation of pulmonary surfactant into the trachea of the spontaneously breathing newborn or premature infant supported by continuous positive airway pressure ventilation.

Neonatal Respiratory Distress Syndrome (NRDS) is caused by endogenous deficiency and/or consumption of pulmonary surfactant (PS) and primarily affects preterm neonates. Many infants with NRDS require tracheal intubation with an endotracheal tube (ETT) for invasive mechanical ventilation (IMV) and PS replacement. ETT and IMV may cause damages to the neonatal lung, setting the stage for the development of long-term respiratory morbidity as bronchopulmonary dysplasia (BPD).

During the last decades perinatal management of very and extremely preterm birth improved. Consequently, most preterm infants start spontaneous breathing after birth, and do not have an obligatory need for ETT and IMV. They can be stabilized with non-invasive ventilation (NIV) modalities of respiratory support, such as Continuous Positive Airway Pressure (CPAP) via nasal prongs or masks, which proved to be as efficacious as ETT with IMV and PS replacement in the management of NRDS. Today, early application of CPAP starting from the delivery room is recommended for the initial management of preterm infants with or at risk for NRDS (SWEET DG. et al. European Consensus Guidelines on the Management of Respiratory Distress Syndrome -2019 Update. Neonatology. 2019; 115:432-450), because it has been proven to decrease the risk of death or BPD in these patients.

The increasing use of NIV as first line treatment for NRDS is related to the discontinuation of PS administration in these patients and this represents a problem. Many premature infants fail CPAP support resulting in delayed PS replacement and prolonged IMV, which increase the risk of mortality and major morbidities as BPD (See DARGAVILLE PA. et al. Incidence and Outcome of CPAP Failure in Preterm Infants. Pediatrics. 2016;138(1):e20153985). To overcome this dilemma, treatment modalities combining NIV with PS administration have been investigated.

The Intubate - SURfactant - Extubate (INSURE) is a well-established treatment strategy that combinines both of these principles by reducing long-term adverse respiratory outcomes, such as BPD, compared to CPAP alone (ISAYAMA T. et al. Noninvasive Ventilation With vs Without Early Surfactant to Prevent Chronic Lung Disease in Preterm Infants: A Systematic Review and Meta-analysis. JAMA Pediatr. 2015; 169:731-739). The INSURE method consists in PS delivering through a planned ETT with a short period of positive pressure ventilation followed by prompt extubating and restoration of CPAP support. The INSURE method has been shown to be efficacious in reducing the need for IMV. However, being still related to a short period of positive pressure ventilation, it has the risk to induce lung injury. Furthermore, this approach has a high failure rate in the most vulnerable newborns, such as those with an extremely low gestational age and weight at birth (DE BISSCHOP B. et al. Early Predictors for Intubation - SURfactant - Extubation Failure in Preterm Infants with Neonatal Respiratory Distress Syndrome: A Systematic Review. Neonatology. 2020; 117:33-45). Therefore, there is still an urgent need to validate further strategies combining NIV with PS replacement.

PS delivery via aerosolisation (RONG H. et al. Nebulized versus invasively delivered surfactant therapy for neonatal respiratory distress syndrome: A systematic review and meta-analysis. Medicine (Baltimore). 2020;25;99(48):e23113), pharyngeal instillation ( ME. et al. Pharyngeal instillation of surfactant before the first breath for prevention of morbidity and mortality in preterm infants at risk of respiratory distress syndrome. Cochrane Database Syst Rev. 2011;16;(3):CD008311) and laryngeal mask (CALEVO MG. et al. Supraglottic airway devices for surfactant treatment: systematic review and meta-analysis. J Perinatal. 2019;39(2): 173-183) are being actively pursued in research, but have not yet been adopted to any significant degree in clinical practice.

PS administration via a thin catheter, also called Less Invasive Surfactant Administration (LISA) method, is becoming increasingly used in neonatal intensive care units worldwide and is now recognized as a viable alternative to the standard mode of PS replacement (HERTNIG E. et al. Less invasive surfactant administration: best practices and unanswered questions. Curr Opin Pediatr. 2020;32(2):228-234). This method involves the introduction of a thin catheter, mainly via the mouth, into the neonatal trachea under direct laryngoscopy. PS is slowly instilled into the tracheobronchial tree from a syringe connected to the thin catheter within 1-2 minutes while the infant is breathing supported by CPAP with a positive end-expiratory pressure set at 6-9 cmH₂O, thus avoiding the need for ETT and IMV in most treated infants. After PS delivery, the catheter is removed from the neonatal trachea and the infant remains supported by CPAP. LISA is not simply an isolated technical procedure for PS delivery but rather part of a comprehensive non-invasive approach supporting the concept of a gentle transition to the extrauterine world enabling preterm infants to benefit from the advantages of spontaneous breathing. Patient comfort and lower complication rates are strong arguments to further investigate and promote the LISA approach.

The LISA method has been shown to be feasible in preterm infants down to a gestational age of 23 completed weeks (KRIBS A. et al. Nonintubated Surfactant Application vs Conventional Therapy in Extremely Preterm Infants: A Randomized Clinical Trial. JAMA Pediatr. 2015;169(8):723-730). Available data suggest that PS delivery through the LISA method decreases the risks of BPD, of death or BPD, and of CPAP failure when compared to PS administration through ETT followed by IMV and to INSURE (RIGO V. et al. Surfactant instillation in spontaneously breathing preterm infants: a systematic review and meta-analysis. Eur J Pediatr. 2016;175(12):1933-1942; ALDANA-AGUIRRE JC. et al. Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis. Archives of Disease in Childhood - Fetal and Neonatal Edition 2017;102: F17-F23). Moreover, the LISA method is the sole approach where some long-term data are available (PORATH M. et al. Surfactant in spontaneous breathing with nCPAP: neurodevelopmental outcome at early school age of infants ≤ 27 weeks. Acta Paediatr. 2011;100(3):352-359). These data show no adverse long-term effects of the LISA method and a trend toward a better neurodevelopmental outcome.

Clinical experiences with the LISA method have been conducted following two main approaches: a) the so-called "Cologne Method", which requires using small Magill's forceps to maneuver and introduce a thin catheter below the neonatal laryngeal vocal cords (KRIBS A. et al. Early administration of surfactant in spontaneous breathing with nCPAP: feasibility and outcome in extremely premature infants (postmenstrual age ≤ 27 weeks). Paediatr Anaesth. 2007;17: 364-369); and b) the so-called "Hobart Method", which requires a 16-G catheter with 1.7 mm outer diameter (Angiocath, cat No. 382259, Becton Dickinson, Sandy, UT, USA) which is semi-rigid and manually guidable, thus obviating the need for Magill's forceps (DARGAVILLE PA. et al. Preliminary evaluation of a new technique of minimally invasive surfactant therapy. Arch Dis Child Fetal Neonatal Ed. 2011;96:F243-F248). Soft catheter introduction without a forceps has been also described as the so-called "Take Care" method (KANMAZ HG. et al. Surfactant administration via thin catheter during spontaneous breathing: randomized controlled trial. Pediatrics 2013; 131: e502-e509).

The fundamental characteristics of a device for the LISA method have not yet been well defined. Ideally, this device should accomplish easy and quick introduction into the small neonatal airway without the need for additional aids, and made of soft material to avoid airway injury and anatomical distortion. In addition, it should be the thinnest as possible to ensure the optimal CPAP pressure transmission, especially in the very preterm infants, and characterized by a clear distal surface marking to ensure the correct positioning of the distal tip within the neonatal trachea under direct laryngoscopy. As far as I know, no device to date fulfill all these requirements.

Different devices have been used until now to deliver PS with the LISA method, such as feeding tubes (with side and central end-holes and an outer diameter of 1.7 mm), suction catheters (with central end-hole and an outer diameter of 1.7 mm), vascular and umbilical catheters (with central end-hole and an outer diameter ranging from 1.3 to 1.7 mm). The majority of these devices are soft, thus requiring Magill's forceps for the introduction into the neonatal airway or special introducers (Neofact® - Lyomark Pharma) (MAIWALD CA. et al. Quick SF: a new technique in surfactant administration. Neonatology 2017; 111:211-213). To date, some straight catheters easy to use orally have also been marketed (LISAcath® - Chiesi Pharmaceuticals; with central end-hole and an outer diameter of 1.7 mm) (SurfcathTM - Vygon Ltd; with central end-hole, an outer diameter of 2.0 mm [body], 0.8 mm [blunted distal end]). The latter devices are also characterized by the apposition by production of depth insertion markers on the distal surface and a centimeter scale on the surface to improve positioning of the distal tip within the neonatal trachea.

According to a recent pan-European survey of more than 300 neonatologists from 37 European countries, standard infant feeding tubes are the most commonly used devices with LISA method (56% of respondents), followed by vascular catheters (34%), and suction catheters (15%) (KLOTZ D. et al. European perspective on less invasive surfactant administration-a survey. Eur J Pediatr. 2017; 176:147-154). The use of Foley catheters, umbilical vessel catheters, neonatal urinary catheters, and custom-made devices has also been reported. Around two-thirds of neonatologists are reported to use Magill's forceps to introduce thin catheters below the laryngeal vocal cords.

There are yet no in vivo comparisons of different catheter insertion methods or types for the LISA method. Rigo et al. (RIGO V. et al. Rigid catheters reduced duration of less invasive surfactant therapy procedures in manikins. Acta Paediatr. 2017; 106:1091-1096) performed a simulation study with different catheters and methods of introduction on intubation manikins. This study found tracheal catheterization with a semirigid or stylet-guided catheter was successfully accomplished in a similar time to ETT and was more rapid than with a flexible tube, with and particularly without Magill's forceps. The failure rate for insertion with each of the catheters was similar (7.5-20%), which was higher than for ETT insertion (no failed insertions). When asked for their subjective evaluation, neonatologists found rigid or stylet-guided catheters the easiest to use.

LISA technique may be also safe and effective for tracheal instillation of other fluid medicaments in infants with NRDS, as steroids and antibiotics. Animal models suggest that tracheal instillation of a low-dose budesonide may diminish the acute lung injury of meconium aspiration syndrome (MOKRA D. et al. Combination of budesonide and aminophylline diminished acute lung injury in animal model of meconium aspiration syndrome. J Physiol Pharmacol. 2008;59 Suppl 6:461-471). Recent meta-analysis designed to evaluate the efficacy and safety of early airway administration of corticosteroids and PS to prevent BPD in premature infants with NRDS reported that early tracheal instillation of corticosteroids using PS as the vehicle is an effective and safe option for preventing BPD, decreasing the additional PS usage and reducing mortality (ZHONG YY. et al. Early lntratracheal Administration of Corticosteroid and Pulmonary Surfactant for Preventing Bronchopulmonary Dysplasia in Preterm Infants with Neonatal Respiratory Distress Syndrome: A Meta-analysis. Curr Med Sci 2019;39:493-499; VENKATARAMAN R. et al. lntratracheal Administration of Budesonide Surfactant in Prevention of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants: A Systematic Review and Meta-Analysis. Pediatr Pulmonol. 2017; 52:968-975). Acute lung injury, such as meconium aspiration syndrome in neonates, may present with exacerbated ventilation and perfusion abnormalities. This can impair the efficacy of intravenous antibiotic therapy in treating pulmonary infection. Tracheal instillation via perfluorochemical agents as a vehicle through microcatheters may adequately deliver drugs, such as the poorly pulmonary-penetrative antibiotic vancomycin, to affect lung regions while maintaining gas exchange and non-toxic serum level. The LISA method may be also used for tracheal instillation of prostacyclin to improve oxygenation without systemic vascular repercussions in infants with persistent pulmonary hypertension supported by NIV (DE JAEGERE AP et al. Endotracheal instillation of prostacyclin in preterm infants with persistent pulmonary hypertension. Eur Respir J. 1998;12(4):932-934).

In the following sections, "proximal" will denote a part that is located near the operator when the latter uses the assembly of the invention, while "distal" will denote a part that is away from the operator during this use.

The assembly of this invention comprises a very thin catheter, hereinafter referred to as "microcatheter", a guidewire and a gripper. Schematically, the function of this assembly is to ensure quick, safe and correct positioning of the distal tip of the microcatheter within the tracheal lumen for effective PS administration without hindering CPAP transmission and spontaneous breathing, thus increasing the patient's tolerability for the procedure, particularly in very and extremely low birth weight infant.

The microcatheter of this assembly comprises a proximal connector and a distal soft composite tube, hereinafter referred to as "tube", with straight, uniform outer diameter ≤ 1 mm (≤ 3 Fr) having proximal and distal ends and a central lumen open at the proximal and distal ends. The connector is hollow, and has proximal and distal ends. The proximal end of the connector is configured to cooperate with a means for the instillation of PS or other fluid medicaments and to allow connection of a threaded plastic cap, and the distal end of the connector is welded to the proximal end of the tube and in fluid communication with its central lumen. The distal end of the tube terminates in a coextruded rounded tip bearing a central end-hole, which is in fluid communication with the central lumen of the tube.

The guidewire of this assembly is stiff-flexible and slidably receptive both into the hollow connector and the central lumen of the tube, to provide rigidity thereto during the introduction of the microcatheter into the infant’s airway and restore softness thereto after its removal from the microcatheter. As used herein "stiff-flexible" refers to the property of the guidewire resulting from its small gauge and material allowing the guidewire to be bent or flexed, with the guidewire providing some resistance to the change in shape. The guidewire has straight, uniform outer diameter not exceeding 0.7 mm (≤ 2.1 Fr), proximal and distal ends and length relative to the length of the microcatheter. The proximal end of the guidewire is welded to a threaded plastic cap adapted to connect with the proximal end of the connector of the microcatheter, and the distal end is rounded. When the guidewire is fully inserted into the microcatheter and the threaded plastic cap screwed around the proximal end of the connector, the guidewire is locked to the microcatheter. This avoids potential airway injury due to the distal end of the guidewire coming out of the central end-hole of the coextruded rounded tip of the tube when introducing the microcatheter into the infant's airway. In addition, the rounded shape of the distal end of the guidewire provides additional guarantees against infant's airway damages as well as against potential ruptures of the thin-walled end of the tube during the introduction of the microcatheter, which further avoids the risk of foreign bodies detaching into the infant's airway. Coating the guidewire with a thin biocompatible silicone film improves its slidability within the microcatheter by preventing the walls of the tube from kinking during its removal from the microcatheter because of the very small outer diameter and the softness of the material. Alternatively, the guidewire can also be sprayed onto the surface with a small amount of biocompatible silicone before the introduction into the microcatheter at the early stage of the assembly preparation.

The gripper of this assembly has a longitudinal medial groove on the rear for its reversible attachment to any point of the tube of the microcatheter internally stiffened by the guidewire. Attaching the gripper to the tube improves the handling of the microcatheter. Moreover, it also acts as a useful reference device onto the microcatheter to help maintain control of the estimated insertion depth while introducing the microcatheter into the infant’s airway under direct laryngoscopy.

Some preferred but non-limiting features of the assembly of this invention are as follows:

the connector of the microcatheter is made of clear, rigid plastic;
the tube of the microcatheter has the outer diameter of 0.8 mm (2.4 Fr) and the length between 15 cm and 25 cm;
the tube of the microcatheter is provided with a sequence of color-coded circumferential bands, colored with complementary colors, on its distal surface near the coextruded rounded tip. These color-coded circumferential bands are sized according to different infant's body weight (preferably three, from ≤ 1 kg to ≥ 3 kg) and arranged from the smallest to the largest infant’s body weight starting from the central end-hole of the coextruded rounded tip and extending proximally along the tube, and with a scale in one-centimeter increments along the surface length starting at 5 centimeters from the central end-hole;
the tube of the microcatheter is made of biocompatible, clear, soft material, preferably polyurethane, or polyvinyl chloride, or high-density polyethylene or flexible polyamide without plasticizer. If the tube of the microcatheter has not clear walls, the tube is preferably of blue color;
the guidewire has the outer diameter of 0.53 mm (1.6 Fr);
the guidewire is made of rigid material, preferably metal as tungsten or nitinol, and is preferably of blue color if the tube has clear walls;
the guidewire is coated with a thin biocompatible silicone film during manufacturing; alternatively, a small amount of biocompatible silicone should be sprayed onto the guidewire by the operator prior to its introduction into the microcatheter;
the gripper is preferably made of semi-hard rubber.

To perform PS administration via the LISA method with the assembly of the present invention, the operator introduces the microcatheter into the infant's airway under direct laryngoscopy by grasping it at the level of the gripper attached to the tube stiffened by the internal guidewire, which was locked to the connector of the microcatheter by screwing the threaded plastic cap, welded to the proximal end of the guidewire, around the proximal end of the connector. Once the chosen color-coded circumferential band, based on the infant's body weight, passes through the laryngeal vocal cords and disappears under the glottic plane, further advancement of the microcatheter is stopped, as the coextruded rounded tip of the tube of the microcatheter is considered placed correctly within the tracheal lumen for effective PS administration. The laryngoscope is then removed from the infant's mouth, the guidewire is unlocked from the connector and removed from the microcatheter. Thereafter, the cone of a syringe filled with the prescribed amount of PS is connected to the proximal end of the connector of the microcatheter and PS is slowly instilled into the neonatal trachea within 1-2 minutes. At the end of the procedure, the microcatheter is removed from the infant's airway. All of the steps of the above-mentioned procedure are performed with the infant breathing autonomously without interrupting CPAP support.

Currently used devices with the LISA method may not ensure safe and effective PS delivery, as suggested by the animal model showing lower alveolar deposition when PS is administered via a thin catheter compared to the INSURE method (NIEMARKT HJ. et al. Effects of less-invasive surfactant administration on oxygenation, pulmonary surfactant distribution, and lung compliance in spontaneously breathing preterm lambs. Pediatr Res 2014;76(2):166-170).

Soft devices, as feeding tubes or umbilical catheters, although they protect against airway injury, require a Magill's forceps or special introducers (Neofact® - Lyomark Pharma) (MAIWALD CA. et al. Quick SF: a new technique in surfactant administration. Neonatology 2017; 111:211-213). Special technical skills are required with these devices and the procedure may be often laborious and potentially harmful due to the increasing patient discomfort, which may result in reflex bradycardia and hypoxemia. Feeding tubes may also lead to inadvertent loss of PS because it partially adheres to the inner surface of the tube due to physical reasons and lack of tube ventilation (DE LUCA D. et al. Surfactant inadvertent loss using feeding catheters or endotracheal tubes. Am J Perinatal 2014; 31: 209-212). Moreover, these tubes as other devices have the disadvantage of side holes rather distant from the distal tip, increasing the risk of PS reflux leading to its inadvertent spillage into the digestive tract. (HERTNIG E. et al. Less invasive surfactant administration: best practices and unanswered questions. Curr Opin Pediatr. 2020; 32:228-234).

Stiff devices as Angiocath, LISAcath® and SurfcathTM, despite ensuring more easy and quick introduction into the infant’s airway without the need of additional aids, increase patient discomfort due to anatomical airway distortion triggering reflex bradycardia and hypoxia. Additionally, the absence of a rounded distal tip (e.g. Angiocath) increases the risk of airway injury with stiff devices. It should also be emphasized that the distal tip of a device used for LISA technique should not be glued or welded on the distal end of the device (e.g. LISAcath®), due to the potential risk of its detachment into the tracheobronchial tree.

Positioning of the distal tip of the device within the neonatal trachea is crucial for effective PS delivery with LISA technique. The distal tip of the device should be positioned inside the tracheal lumen at an adequate height, hereinafter referred to as “optimum height”, between the laryngeal vocal chords and the tracheal carina to prevent both PS reflux into the digestive tract and asymmetric release of PS into the bronchial tree. In general, it is recommended to introduce the distal tip of the device 1-2 cm below the laryngeal vocal cords (HERTNIG E. et al. Less invasive surfactant administration: best practices and unanswered questions. Curr Opin Pediatr. 2020; 32:228-234). However, this indication may be too generic due to the shortened length of the neonatal trachea, the variability of its size at various gestational ages, and the difficulties encountered under direct laryngoscopy (e.g. narrowing of the visual field; fluid secretions; blurred vision). Visualizing the passage of a depth marker positioned on the distal end of the device through the laryngeal vocal cords under direct laryngoscopy is undoubtedly the best way to ensure positioning of the distal tip at the optimum height within the neonatal trachea. To improve this, the operator often applies custom-made depth markers onto the surface of the distal end of the device. However, this affects sterility and poses the risk of foreign bodies detaching inside the neonatal trachea. On the other hand, when depth markers are available by the manufacturing process (e.g. LISAcath®) these may result confusing for the operator, as reported in a recent study (FABBRI L. et al. Five national mannequin studies found that neonatologists preferred to use LISAcath rather than Angiocath for the administration of less invasive surfactants. Acta Paediatr. 2018; 107: 780-783) or lead to a deep positioning of the distal tip in the extremely low birth weight infants (e.g. SurfcathTM). The scale in one-centimeter increments printed on the surface of several marketed devices (LISAcath®; SurfcathTM) is often used to establish the insertion depth into the infant’s airway as for ETT according to the following rule: the estimated insertion depth of the distal tip of the device from the labial commissure of the infant's mouth = infant's body weight (expressed in kilograms) + 6 cm. However, is not recommended to rely only on this scale to ensure positioning of the distal tip at the optimum height within the neonatal trachea because of anatomical reasons. In fact, tracheal tubes have larger outer diameters than the thin catheters used in the LISA method, which provide greater rigidity to the former and make them less displaceable by neonatal tongue after ETT. Instead, thin catheters used in the LISA technique are more easily displaced posteriorly by neonatal tongue, which may lead to inadvertent rise of the distal tip of the catheter during PS instillation, causing oesophageal spillage of PS. More conveniently, the scale in one-centimeter increments should be used to assess/refine the distal tip positioning before PS administration.

Pressure transmission from CPAP support appears seriously impaired or even close to zero during PS administration with currently used devices for the LISA method, as demonstrated in a modelling study (JOURDAIN G. et al. Continuous positive airway pressure delivery during less invasive surfactant administration: a physiologic study. J Perinatal 2018;38:271-277). Thin catheters used in the LISA method represent non-ventilable tubes that can adversely affect neonatal respiratory function by decreasing cross-sectional area of the upper airway available for spontaneous breathing and increasing airway resistances during the procedure (MATSUSHIMA Y. et al. Alterations in pulmonary mechanics and gas exchange during routine fiberoptic bronchoscopy. Chest 1984;86:184-188). Increased airway resistance is more prominent in infants than in adults given the likelihood of crying, small trachea size and airflow turbulence due to the imperfect circular shape of the neonatal airway. Only about 30% of neonates undergoing the LISA method receive adequate analgesia or sedation (MEHLER K. et al. Use of analgesic and sedative drugs in VLBW infants in German NICUs from 2003-2010. Eur J Pediatr 2013; 172:1633-1639). Therefore, intense crying is more likely to occur during PS administration via the LISA method in these infants, profoundly affecting patient's discomfort and respiratory function. For the sake of our discussion, a tracheal diameter of less than 3 mm can be found in a considerably large, although variable, proportion of preterm neonates younger than 28 weeks' gestation - i.e., those who are at high risk of negative respiratory outcomes and need careful respiratory support. Based on their outer diameters, currently used thin catheters for the LISA method reduce the upper airway cross-sectional area available for CPAP transmission and spontaneous breathing from 30 - 40% up to 70% in the very and extremely low birth weight infants, respectively (JIT H. et al. Dimensions & shape of the trachea in the neonates, children & adults in northwest India. Indian J Med Res 2000;112: 27-33; FAYOUX P. et al. Determination of endotracheal tube size in a perinatal population: an anatomical and experimental study. Anesthesiology 2006;104: 9546-9560; WANI TM. et al. Upper airway in infants-a computed tomography-based analysis. Paediatr Anaesth 2017;27:501-505). A further reduction of this area due to the narrowing of the neonatal airway at the cricoids’ ring should be also considered.

An assembly comprising a microcatheter, characterized by a biocompatible very thin tube ending with a coextruded rounded tip bearing a central end hole, that is internally stiffened by a rigid guidewire, locked to the microcatheter to guarantee easy and safe introduction into the infant’s airway, equipped with distal depth marking clearly visible under direct laryngoscopy, based on different infant’s body weight, and a gripper attached to the microcatheter to improve handling as well as acting as an additional control of the insertion depth, may solve all the technical issues related to the currently used devices for the LISA method.

The straight, uniform outer diameter ≤ 1 mm (≤ 3 Fr) of the tube of the microcatheter ensures the optimal airway patency for CPAP transmission with minimal increase in airway resistance, even in the very and extremely low birth weight infant with variable tracheal diameters, lowering patient's respiratory workload and discomfort during the LISA procedure. The inadvertent PS loss is also reduced by using this very thin catheter due to physical reasons. The coextruded rounded tip of the tube prevents airway injury during introduction and avoids the risk of detachment within the tracheobronchial tree during the procedure. The central end-hole of the coextruded rounded tip provides more effective and waste-free PS delivery. Potential obstruction related to PS administration through a central end-hole in thin catheters is not supported by clinical evidence. Similarly, fear of potential lung damage from expelling PS or other drug solution through the central end-hole in a very thin catheter appears unwarranted if PS administration is slowly performed as prescribed in the LISA method.

Stiffening the tube of the microcatheter by an internal guidewire facilitates its rapid insertion into the infant’s airway without the need for additional aids, even in very and extremely low birth weight infant. The very small gauge and softness of the tube of the microcatheter dictates the guidewire to be positioned solely within a central lumen, the same used to deliver PS, as other placements would not ensure adequate resistance to such a thin tube against potential for bending and kinking during the introduction of the microcatheter into the infant's airways. The locking of the guidewire to the microcatheter prevents from airway injury by impeding the distal end of the guidewire from coming out of the central end-hole of the coextruded rounded tip of the tube during the introduction. Moreover, the rounded shape of the distal end of the guidewire further protects against airway injury and potential ruptures of the thin-walled distal end of the tube during the introduction into the infant’s airway, avoiding the risk of foreign bodies detaching within the neonatal trachea. The removal of the guidewire from the central lumen of the tube, facilitated by its thin silicone coating, allows the tube of the microcatheter to adapt to the infant's airway during PS delivery, avoiding significant anatomical distortions during the instillation of PS that increases patient's tolerability for the procedure.

The gripper attached to the tube of the microcatheter improves its handling and provides a reference device to help the operator maintain constant control of the estimated insertion depth while introducing the microcatheter into the infant’s airway under direct laryngoscopy. This is accomplished by hooking the gripper onto the microcatheter at an adequate distance [= infant's body weight (expressed in kilograms) + 6 cm] from the distal tip by using the scale in one-centimeter increments on the surface of the tube of the microcatheter, which prevents too deep or too high depth insertion into the neonatal trachea. Taking into consideration the potential posterior displacement of the microcatheter due to the neonatal tongue, it may be considered adding half to one centimeter to the above-mentioned measurement when attaching the gripper to the microcatheter. Further assessment/refinement of the insertion depth of the microcatheter may be also performed before PS delivery by taking into the account the distance between the gripper and the labial commissure of the infant’s mouth.

Issue pertaining the difficulty in establishing the correct insertion depth positioning of the distal tip of the device under direct laryngoscopy is solved by adding several color-coded circumferential bands (at least three), colored with complementary colors, on the distal surface of the tube of the microcatheter. The size and arrangement of these color-coded circumferential bands can be borrowed from the depth markers printed on the distal end of neonatal tracheal tubes that are calibrated according to different infant’s body weight (from ≤ 1 kg to ≥ 3 kg), whose efficacy has been confirmed by the clinical practice. Using complementary colors also improves the visibility of these color-coded circumferential bands, due to the mutual improvement of the color brightness by proximity. Staining of the device can also improve visualization under direct laryngoscopy. Alternatively, this can be achieved by using a colored guidewire, preferably of blue, if the tube of the microcatheter has transparent walls.

The foregoing aspects and other features of the invention are explained in the following description, taken in connection with the accompanying drawings, wherein:

is an elevation view illustrating the features of the assembly of the present invention prepared for introduction into the infant's trachea. The gripper is shown attached to the tube of the microcatheter at a distance between its distal edge and the coextruded rounded tip corresponding to 6 centimeters plus the body weight (expressed in kilograms) of the infant who will receive PS via the LISA method. Taking into consideration the potential displacement of the microcatheter due to the neonatal tongue, it may be considered adding half to one centimeter to the above-mentioned measurement when attaching the gripper to the microcatheter. The guidewire has been introduced within the hollow connector and the central lumen of the tube of the microcatheter to stiffen the tube and is clearly visible throughout the entire length of the clear walls of both the connector and tube of the microcatheter because of its blue color. The threaded plastic cap welded to the proximal end of the guidewire is screwed around the proximal end of the connector of the microcatheter to lock the guidewire before the introduction of the microcatheter. Also shown are the sequence of the three color-coded circumferential bands on the distal surface of the tube of the microcatheter near the coextruded rounded tip, and the scale in one-centimeter increments along the surface length of the tube. The outer diameter of the tube and the inner diameter of the central lumen and of the central end-hole of the coextruded rounded tip are reported;

is an elevation view, similar to , illustrating the guidewire partially withdrawn from the microcatheter once the threaded plastic cap has been unscrewed from the proximal end of the connector of the microcatheter unlocking the guidewire therefrom;

is a perspective view of the distal end of the tube of the microcatheter having the guidewire introduced into the central lumen, illustrating the sequence of the three color-coded circumferential bands used for positioning the coextruded rounded tip of the microcatheter within the tracheal lumen. The color-coded circumferential bands are near the coextruded rounded tip, bearing the central end hole, are sized according to three different infant’s body weight (ranging from ≤ 1 kg to ≥ 3 kg) and arranged from the smallest to the largest infant’s body weight starting from the central end-hole of the coextruded rounded tip and extending proximally on the tube of the microcatheter;

is an elevation view of the rear of the gripper illustrating the longitudinal medial groove for the attachment to the tube of the microcatheter;

is an elevation view of the rear of the gripper showing a section of the tube of the microcatheter, internally stiffened by the guidewire, engaged within the longitudinal medial groove of the gripper;

is a cross-sectional view of the upper airway and oesophagus of an autonomously breathing infant with NRDS supported by CPAP via a nasal interface applied to the nostrils. The optimum height within the tracheal lumen where the coextruded rounded tip of the tube of the microcatheter must be positioned for effective PS delivery, to avoid both asymmetric distribution into the bronchial tree and oesophageal spillage, is shown;

is a cross-sectional view of the same infant of after the laryngoscope blade has been placed into his/her mouth, illustrating the coextruded rounded tip of the tube of the microcatheter reaching the optimum height within the tracheal lumen for effective PS administration;

is a cross-sectional view of the same infant of , after the laryngoscope blade has been removed from his/her mouth, illustrating the tube of the microcatheter adapting to the infant's airway as the guidewire is removed from the microcatheter;

is a cross-sectional view of the same infant of after the guidewire has been removed from the microcatheter, illustrating a syringe filled with the prescribed amount of PS connected to the proximal end of connector of the microcatheter for slow tracheal instillation through the microcatheter, according to the LISA method.

In this section, we shall explain this invention with reference to the appended drawings. The assembly of the invention will be more particularly described in the case of the tracheal instillation of PS preferably in very and extremely low birth weight infant. However, this is not limiting as the assembly can be used for instilling other types of fluid medicaments and/or be used for adults.

Referring herein mainly to and , until otherwise indicated, the assembly (1) of this disclosure comprises a microcatheter (2), a guidewire (4) and a gripper (17).

The microcatheter (2) comprises a proximal connector (8) and a distal tube (3) of straight, uniform and very small gauge [outer diameter (11): ≤ 1 mm; preferably of 0.8 mm] having proximal and distal ends and a central lumen open at the proximal and distal ends. The connector (8) is hollow and has proximal and distal ends, the proximal end being configured to cooperate with the tip of a syringe containing PS, as shown in , and to allow connection of a threaded plastic cap (5) welded to the proximal end of the guidewire (4), as shown in and . The distal end of the connector (8) is welded to the proximal end of the tube (3) and is in fluid communication with its central lumen. The connector (8) can be of the Luer, Luer Lock type or any connector conforming to the standards in force. Suitable material for the connector (8) is preferably clear, rigid plastic. The distal end of the tube (3) terminates in a coextruded rounded tip (9) having a central end-hole (10) with an inner diameter (12) not exceeding 0.7 mm. The central end-hole (10) is in fluid communication with the central lumen of the tube (3) of the microcatheter (2). Suitable biocompatible soft materials for the tube (3) of the microcatheter (2) include polyurethane, polyvinyl chloride, high-density polyethylene and flexible polyamide without plasticizer. The walls of the tube (3) are preferably clear, as also shown in , , , and .

Due to its very small gauge, the tube (3) of the microcatheter (2) ensures the optimal airway patency for CPAP (C) transmission with minimal increase of the airway resistance, thus lowering the respiratory workload and patient discomfort during the LISA procedure, particularly in very and extremely low birth weight infant, as shown in , and . The coextruded rounded tip (9) of the tube (3) of the microcatheter (2) prevents airway injury and the risk of foreign bodies detaching into the neonatal trachea. Moreover, after the removal of guidewire (4) from the microcatheter (2), the tube (3) adapts to the infant's airway due to its softness, avoiding significant anatomical distortions during PS instillation, as shown in and , thus increasing patient’s tolerability for the procedure.

The guidewire (4) has a straight, uniform and very small gauge (outer diameter: ≤ 0.7 mm; preferably of 0.53 mm), with proximal and a distal ends and length relative to the microcatheter (2). The guidewire (4) is stiff-flexible and slidably receptive into the hollow connector (8) and the central lumen of the tube (3) of the microcatheter (2). The proximal end of the guidewire (4) is welded to a threaded plastic cap (5) and the distal end has a rounded shape. The threaded plastic cap (5) can be screwed around the proximal end of the connector (8) of the microcaheter (2), as shown in and in , or unscrewed therefrom, as shown in and in . By screwing the threaded plastic cap (5) around the proximal end of the connector (8) the guidewire (4) is locked (6) for safe introduction of the microcatheter (2) into the infant’s airway. The guidewire (4) is colored, preferably of blue, to improve visualization of the microcatheter (2) under direct laryngoscopy (19), as shown in , due to the clear walls of the tube (3). The guidewire (4) is made of rigid material, the most suitable being metal, particularly tungsten or nitinol. The guidewire (4) is coated with a thin biocompatible silicone film added during manufacturing that improves its slidability within the microcatheter (2), which prevents the walls of the tube (3) from kinking, especially during the removal from the microcatheter (2), due to the very thin outer diameter (11) and softness of the tube (3), as shown in .

The guidewire (4) stiffens the tube (3) of the microcatheter (2) for its easy and quick introduction into the infant's airway without the need for additional aids, even in very and extremely low birth weight infant, avoiding significant kinking and/or bending. Due to its small gauge, the guidewire (4) is also enough flexible to avoid airway injury. The operator can shape the assembly (1) by bending it distally in the most difficult cases, exploiting the rigidity of the guidewire (4). The locking (6) of the guidewire (4) to the connector (8) of the microcatheter (2) prevents the distal end from coming out of the central end-hole (10) of the coextruded rounded tip (9) during the introduction into the infant’s airway under direct laryngoscopy (19), as shown in , avoiding potential airway injury. Moreover, the rounded shape of the distal end of the guidewire (4) prevents against potential airway injury during the introduction of the microcatheter (2) and ruptures of the thin-walled distal end of the tube (3), further avoiding the risk of foreign bodies detaching within the neonatal trachea.

shows the rear of the gripper (17), preferably made of semi-hard rubber, with the longitudinal medial groove (20) adapted to engage with a portion of the tube (3) when internally stiffened by the guidewire (4). The gripper (17) can be attached in a reversible way to any point of the tube (3) of the microcatheter (2) by pressing a portion of the tube (3) against the longitudinal medial groove (20) until it is fully engaged inside, as more clearly shown in . Care should be taken in placing the distal edge (21) of the gripper (17) at a distance (18) from the rounded tip (9) equal to 6 cm plus the infant's body weight (expressed in kilograms), using the scale (13) in one-centimeter increments along the surface length of the tube (3) as a reference, as shown in and . Taking into consideration the potential posterior displacement of the tube (3) of the microcatheter (2) due to the neonatal tongue, it may be considered adding half to one centimeter to the above-mentioned measurement (18) when attaching the gripper (17) to the microcatheter (2). This prevents the coextruded rounded tip (9) from being inserted too distally into the infant's airway, because the operator stops any further advancement of the microcatheter (2) once the gripper (17) reach the labial commissure of the mouth (M) of the infant (P), as shown in , and . Similarly, a deficit of insertion should be considered if the distal edge (21) of the gripper (17) remains too far from the infant's mouth (M) at the end of the introduction of the microcatheter (2). If necessary, further adjustments of the insertion depth can be performed before PS administration using the scale in one-centimeter increments (13) as a reference.

Attaching the gripper (17) to the tube (3) of the microcatheter (2) improves handling of the microcatheter (2), which may be difficult because of the very small outer diameter (11) of the tube (3). Moreover, the gripper (17) provides a useful reference device on the microcatheter (2) to help the operator maintaining constant control of the estimated insertion depth (18), as shown in and , while introducing the microcatheter (2) into the infant’s airway under direct laryngoscopy (19), as shown in .

illustrates, with more detail respect to in , , , and , the sequence of the color-coded circumferential bands (preferably three) (14 15 16) located on the distal surface of the tube (3) for determining the insertion depth of the coextruded rounded tip (9) under direct laryngoscopy. These color-coded circumferential bands (14 15 16), colored with complementary colors, are sized according to three different infant’s body weights (from ≤ 1 kg to ≥ 3 kg) and arranged from the smallest to the largest infant’s body weight starting from the central end-hole (10) of the coextruded rounded tip (9) and extending proximally on the tube (3).

The choice and arrangement of these three color-coded circumferential bands (14 15 16) depend on their optimal visibility under direct laryngoscopy (19), as shown in , due to the mutual improvement of brightness of the complementary colors by proximity. The color-coded circumferential bands (14 15 16) aim to ensure placement of the coextruded rounded tip (9) at the optimum height (H) within the tracheal lumen (T), to prevent both asymmetrical administration of PS into the tracheobronchial tree (B) (due to a deep positioning) and esophageal spillage (E) (due to a high positioning), as shown in , , and . The sizes of these three color-coded circumferential bands (14 15 16) shown in , , , , and are borrowed from the distal depth markers of the commonly used neonatal tracheal tubes available for different infant’s body weight (from ≤ 1 kg to ≥ 3 kg). Proceeding proximally from the coextruded rounded tip (9) on the tube (3) of the microcatheter (2), the arrangement of the color-coded circumferential bands (14 15 16) follows this order:

the first color-coded circumferential band (14), preferably of bright purple, extends 1.8 cm proximally along the surface of the tube (3) from the central end-hole (10) of the coextruded rounded tip (9), representing the optimum height (H) inside the tracheal lumen (T) below the laryngeal vocal cords (V) for an infant weighing 1 kg or less, as shown in , , and ;
the second color-coded circumferential band (15), preferably of bright yellow, extends 0.5 cm proximally along the surface of the tube (3) from the proximal edge of the first color-coded circumferential band (14), representing the optimum height (H) inside the tracheal lumen (T) below the laryngeal vocal cords (V) for an infant weighing between 1 kg and 2 kg, as shown in , , and ;
the third color-coded circumferential band (16), preferably of bright red, extends 0.5 cm proximally along the surface of the tube (3) from the proximal edge of the second color-coded circumferential band (15), representing the optimum height (H) inside of the tracheal lumen (T) below the laryngeal vocal cords (V) for an infant weighing 3 kg or more, as shown in , , and .

Examples

Herein it is briefly described the LISA method performed with the assembly (1) of this disclosure.

illustrates a spontaneously breathing infant (P) weighing 1 kg supported by CPAP (C) through an interface (I) applied to the nostrils (N) who need to receive PS via the LISA method to treat NRDS. Anatomical landmarks as laryngeal vocal cords (V), main bronchial tree (B), oesophagus (E) and the optimum height (H) within the tracheal lumen (T) where the coextruded rounded tip (9) of the tube (3) of the microcatheter (2) should be positioned for effective PS delivery are shown.

The operator prepares the assembly (1) of this disclosure by introducing the guidewire (4) into the hollow connector (8) and making it sliding into the central lumen of the tube (3) of the microcatheter (2) until the threaded plastic cap (5) meets the proximal end of the connector (8). If the guidewire (4) is not coated with a thin biocompatible silicone film during manufacturing, the operator may spray a small amount of biocompatible silicone onto the surface of the guidewire (4) prior to its introduction into the microcatheter (2). At this point, the operator screws the threaded plastic cap (5) around the proximal end of the connector (8) to lock (6) the guidewire (4) for safe introduction, as particularly shown in . Thereafter, the operator attaches the gripper (17) on the microcatheter (2) by pressing a portion of the tube (3) internally stiffened by the guidewire (4) against the longitudinal medial groove (20) on the rear of the gripper (17) until the portion of the tube (3) is fully engaged inside it, as particularly shown in . In doing this, the operator pays particular attention in placing the distal edge (21) of the gripper (17) at a distance (18) equal to 7 cm from the coextruded rounded tip (9) of the tube (3) of the microcatheter (2) using the scale in one-centimeter increments (13) on the surface of the tube (3) as a reference, as particularly shown in and . This, among other things, will help the operator maintaining the constant control of the estimated insertion depth (18) while introducing the microcatheter (2) into the infant's airway under direct laryngoscopy (19). Taking into consideration the posterior displacement of the tube (3) of the microcatheter (2) due to the neonatal tongue, it may be appropriate to add half to one centimeter to the above measurement (18) when attaching the gripper (17) to the microcatheter (2).

Referring now to , the operator introduces the laryngoscope blade (22) using the left hand (L) into the mouth (M) of the same infant (P) of to visualize the laryngeal vocal cords (V) under direct laryngoscopy (19) without interrupting CPAP (C) support applied to the nostrils (N) via the interface (I). By grasping the microcatheter (2) at the gripper (17) with the right hand (R), the operator makes the coextruded rounded tip (9) of the tube (3) of the microcatheter (2) enter the tracheal lumen (T), making it sliding through the laryngeal vocal cords (V) of the newborn. Once the proximal edge of the first color-coded circumferential band (14) disappears under the laryngeal vocal cords (V), the operator stops any advancement of the microcatheter (2), as the coextruded rounded tip (9) of the tube (3) of the microcatheter (2) is now supposed to be at the optimum height (H) within the tracheal lumen (T) for PS delivery, which avoids both asymmetric administration into the bronchial tree (B) and oesophageal leakage (E).

Referring now to , the operator takes off the laryngoscope blade (22) from the mouth (M) of the same infant (P) of using the left hand (L), while firmly holding the gripper (17) at the labial commissure of the infant's (P) mouth (M) using the right hand (R). At this point, the operator checks the position of the distal edge (21) of the gripper (17) relative to the labial commissure of the mouth (M) of the infant (P). If necessary, a further refinement of the insertion depth of the microcatheter (2) is performed, based on the estimated insertion depth (18), as shown in and , using the scale in one-centimeter increments (13) on the surface of the tube (3) of the microcatheter (2) as a reference. Once confirmed that the coextruded rounded tip (9) of the tube (3) of the microcatheter (2) has been placed at the optimum height (H) within the tracheal lumen (T) to prevent either PS asymmetric administration (B) and oesophageal leakage (E), the operator unscrews the threaded plastic cap (5) from the connector (8) of the microcatheter (2) to unlock (7) the guidewire (4) therefrom. Thereafter, the operator removes the guidewire (4) from the microcatheter (2) using the left hand (L), while still holding firmly the gripper (17) to the labial commissure of the mouth (M) of the newborn (P) with the right hand (R) without interrupting the CPAP (C) support applied to the nostrils (N) through the interface (I).

Referring now to , the tip of a syringe (23) filled with the prescribed amount of PS heated to body temperature plus an additional 1 ml of air is connected to the connector (8) of the microcatheter (2). PS is then slowly delivered (S) at the coextruded rounded tip (9) of the tube (3) of the microcatheter (2) within the tracheal lumen (T) in 1-2 minutes, while the spontaneously breathing infant (P) remains supported by CPAP (C) applied to the nostrils (N) through the interface (I). At the end of the procedure, the microcatheter (2) is removed and the infant (P) remains supported by CPAP (C), as shown in .

In the preceding detailed description, specific embodiments are described. As various modifications and changes could be made thereto without departing from the broader spirit and scope of the invention, it is intended that all matter contained in the description above or shown in the accompanying drawings should be interpreted as illustrative and not in a limiting sense.

Claims

An assembly (1) for the instillation of one or more fluid medicaments into a conduit of a person while spontaneous breathing is allowed, particularly the conduit being the trachea (T) and the person a newborn or premature infant (P) supported by CPAP (C) receiving pulmonary surfactant, the assembly (1) comprising:
- a microcatheter (2), the microcatheter (2) comprising a connector (8) and a soft composite tube (3), the connector (8) being preferably made of rigid, clear plastic, the soft composite tube (3) being characterized by a very small outer diameter (11), a coextruded rounded tip (9) with a central end-hole (10), a sequence of color-coded circumferential bands (14 15 16) near the coextruded rounded tip (9) and a scale in one-centimeter increments (13) along the surface;
- a guidewire (4), the guidewire (4) having proximal and distal ends and length relative to the microcatheter (2), the proximal end being welded to a threaded plastic cap (5) and the distal end rounded, wherein the guidewire (4) being characterized in that being stiff-flexible and slidably receptive into the microcatheter (2); and
- a gripper (17), the gripper (17) having a longitudinal medial groove (20) on the rear and being characterized by the reversible attachment to any point of the soft composite tube (3) of the microcatheter (2) when internally stiffened by the guidewire (4).
The microcatheter (2) of claim 1, wherein the soft composite tube (3) having proximal and distal ends and a central lumen open at the proximal and distal ends, the distal end terminating in the coextruded rounded tip (9) avoiding airway injury and detachment of foreign bodies during the introduction of the microcatheter (2) into the neonatal trachea (T), and wherein the central end-hole (10) being in fluid communication with the central lumen, and wherein the outer diameter (11) being straight, uniform and not exceeding 1 mm (≤ 3 Fr), preferably 0.8 mm (2.4 Fr), to allow optimal CPAP (C) transmission, especially in the very and extremely low birth weight infants, and further wherein the sequence of color-coded circumferential bands (14 15 16) being colored with complementary colors, and sized and arranged according to different infant’s body weights, preferably three.
The microcatheter (2) of claim 1, wherein the connector (8) being hollow with proximal and distal ends, the proximal end being configured to allow the connection of the threaded plastic cap (5) and of a means for the instillation into the trachea (T) of pulmonary surfactant and other fluids medicaments (23), the distal end being welded to the proximal end of the soft composite tube (3) and in fluid communication with the central lumen of the soft composite tube (3).
The microcatheter (2) of claim 1, wherein the sequence of color-coded circumferential bands (14 15 16) comprising:
- a first color-coded circumferential band (14), the first color-coded circumferential band (14) ensuring the position of the coextruded rounded tip (9) at the optimum height (H) within the neonatal trachea (T) for infants weighing ≤ 1 kg, characterized by being preferably of bright purple and extending 1.8 cm proximally along the surface of the soft composite tube (3) from the central end-hole (10) of the coextruded rounded tip (9);
- a second color-coded circumferential band (15), the second color-coded circumferential band (15) ensuring the position of the coextruded rounded tip (9) at the optimum height (H) within the neonatal trachea (T) for infants weighing between 1 kg and 2 kg, characterized by being preferably of bright yellow and extending 0.5 cm proximally along the surface of the soft composite tube (3) from the proximal edge of the first color-coded circumferential band (14); and
- a third color-coded circumferential band (16), the third color-coded circumferential band (16) ensuring the position of the coextruded rounded tip (9) at the optimum height (H) within the neonatal trachea (T) for infants weighing ≥ 3 kg, characterized by being preferably of bright red and extending 0.5 cm proximally along the surface of the soft composite tube (3) from the proximal edge of the second color-coded circumferential band (15).
The microcatheter (2) of claim 1, wherein the soft composite tube (3) being made of biocompatible material, preferably polyurethane, or polyvinyl chloride, or high-density polyethylene or flexible polyamide without plasticizer, to avoid anatomical distortion of the neonatal trachea (T) during the instillation of pulmonary surfactant and other fluid medicaments (23), and wherein being between 15 and 25 cm in length.
The microcatheter (2) of claim 1, wherein the walls of the soft composite tube (3) are preferably clear or blue colored, to improve visualization under direct laryngoscopy (19).
The assembly (1) of claim 1, wherein the guidewire (4) having straight, uniform outer diameter not exceeding 0.7 mm (≤ 2.1 Fr), preferably 0.53 mm (1.6 Fr), and wherein the locking (6) of the guidewire (4) to the connector (8), obtained by screwing the threaded plastic cap (5) around the proximal end of the connector (8), and the rounded distal end of the guidewire (4) preventing airway injury and ruptures of the soft composite tube (3) during the introduction of the microcatheter (2) into the neonatal trachea (T).
The assembly (1) of claim 1, wherein the guidewire (4) being made of rigid material, preferably metal such as tungsten or nitinol, to facilitate the introduction of the microcatheter (2) into the infant’s airway by providing rigidity to the soft composite tube (3), and wherein the removal of the guidewire (4) restoring softness to the soft composite tube (3) during the instillation of pulmonary surfactant and other fluid medicaments (23) into the neonatal trachea (T), and wherein being colored, preferably of blue, if the walls of soft composite tube (3) are clear, to improve visualization under direct laryngoscopy (19).
The assembly (1) of claim 1, wherein the guidewire (4) being coated with a thin biocompatible silicone film, preferably during manufacturing, to prevent the walls of the soft composite tube (3) from kinking during its removal from the microcatheter (2).
The assembly (1) of claim 1, wherein the longitudinal medial groove (20) of the gripper (17) being sized to engage within it a portion of the soft composite tube (3) internally stiffened by the guidewire (4) to facilitate handling of the microcatheter (2).
The assembly (1) of claim 1, wherein the attachment of the gripper (17) on the soft composite tube (3) of the microcatheter (2), using the scale in one-centimeter increments (13) as a reference, allows the operator to maintain constant control of the estimated insertion depth (18) of the microcatheter (2) during its introduction into the infant’s airway under direct laryngoscopy (19).
The assembly (1) of claim 1, wherein the gripper (17) being preferably made of semi-hard rubber.