Mechanical complications after central venous catheterisation in the ultrasound-guided era: a prospective multicentre cohort study.

BACKGROUND: Limited data are available on the incidence of mechanical complications after ultrasound-guided central venous catheterisation. We aimed to determine the incidence of mechanical complications in hospitals where real-time ultrasound guidance is clinical practice for central venous access and to identify variables associated with mechanical complications. METHODS: All central venous catheter insertions in patients ≥16 yr at four emergency care hospitals in Sweden from March 2, 2019 to December 31, 2020 were eligible for inclusion. Every insertion was monitored for complete documentation and occurrence of mechanical complications within 24 h after catheterisation. Multivariable logistic regression analyses were used to determine associations between predefined variables and mechanical complications. RESULTS: In total, 12 667 catheter insertions in 8586 patients were included. The incidence (95% confidence interval [CI]) of mechanical complications was 7.7% (7.3-8.2%), of which 0.4% (0.3-0.5%) were major complications. The multivariable analyses showed that patient BMI <20 kg m-2 (odds ratio 2.69 [95% CI: 1.17-5.62]), male operator gender (3.33 [1.60-7.38]), limited operator experience (3.11 [1.64-5.77]), and increasing number of skin punctures (2.18 [1.59-2.88]) were associated with major mechanical complication. Subclavian vein catheterisation was associated with pneumothorax (5.91 [2.13-17.26]). CONCLUSIONS: The incidence of major mechanical complications is low in hospitals where real-time ultrasound guidance is the standard of care for central venous access. Several variables independently associated with mechanical complications can be used for risk stratification before catheterisation procedures, which might further reduce complication rates. CLINICAL TRIAL REGISTRATION: NCT03782324.

Nebulization of High-Dose Poractant Alfa in Newborn Piglets on Nasal Continuous Positive Airway Pressure Yields Therapeutic Lung Doses of Phospholipids.

OBJECTIVE: It is not known how much surfactant must be nebulized to reach a lung dose of phospholipids equivalent to that obtained by the instillation of 200 mg/kg of surfactant. We aimed to assess the feasibility of nebulizing a high-dose of poractant alfa with the eFlow-Neos investigational vibrating-membrane nebulizer in newborn piglets on nasal continuous positive airway pressure (nCPAP) and to determine whether this intervention would yield therapeutic lung doses of phospholipids. STUDY DESIGN: Twelve 1-day-old piglets on nCPAP received 600 mg/kg of poractant alfa admixed with technetium-99m via nebulization. Six piglets receiving 200 mg/kg of instilled synthetic surfactant served as controls. Lung deposition (percentage of the nominal dose) was determined by gamma scintigraphy, and the phospholipids' lung dose was calculated. RESULTS: The lung dose of phospholipids (mean ± standard deviation [SD]) was 138 ± 96 mg/kg with nebulization, and 172 ± 24 mg/kg with instillation (p = 0.42). Nebulization took 58 ± 12 minutes. The arterial partial pressure of carbon dioxide increased from 6.7 ± 1.1 to 7.2 ± 1.1 kPa during nebulization (p = 0.04). Cerebral oximetry remained stable, and there was no hemodynamic instability. CONCLUSION: Nebulization was well tolerated, and the mean lung dose of phospholipids was above 100 mg/kg, that is, not different from the instillation group. These experimental findings suggest that it may be feasible to reach therapeutic lung doses of phospholipids by surfactant nebulization during nCPAP. KEY POINTS: · It is not known if effective lung doses of surfactant can be delivered by nebulization.. · Nebulization of high-dose surfactant in newborn piglets on nCPAP was well tolerated.. · A high-dose of nebulized poractant alfa yielded therapeutic lung doses of phospholipids..

Lung Deposition of Surfactant Delivered via a Dedicated Laryngeal Mask Airway in Piglets.

It is unknown if the lung deposition of surfactant administered via a catheter placed through a laryngeal mask airway (LMA) is equivalent to that obtained by bolus instillation through an endotracheal tube. We compare the lung deposition of surfactant delivered via two types of LMA with the standard technique of endotracheal instillation. 25 newborn piglets on continuous positive airway pressure support (CPAP) were randomized into three groups: 1-LMA-camera (integrated camera and catheter channel; catheter tip below vocal cords), 2-LMA-standard (no camera, no channel; catheter tip above the glottis), 3-InSurE (Intubation, Surfactant administration, Extubation; catheter tip below end of endotracheal tube). All animals received 100 mg·kg-1 of poractant alfa mixed with 99mTechnetium-nanocolloid. Surfactant deposition was measured by gamma scintigraphy as a percentage of the administered dose. The median (range) total lung surfactant deposition was 68% (10-85), 41% (5-88), and 88% (67-92) in LMA-camera, LMA-standard, and InSurE, respectively, which was higher (p < 0.05) in the latter. The deposition in the stomach and nasopharynx was higher with the LMA-standard. The surfactant deposition via an LMA was lower than that obtained with InSurE. Although not statistically significant, introducing the catheter below the vocal cords under visual control with an integrated camera improved surfactant LMA delivery by 65%.

Impact of Body Position on Lung Deposition of Nebulized Surfactant in Newborn Piglets on Nasal Continuous Positive Airway Pressure.

INTRODUCTION: The ideal body position during surfactant nebulization is not known. OBJECTIVE: The aim of this study was to determine whether body positioning during surfactant nebulization influences surfactant distribution and deposition in the lungs. METHODS: Twenty-four 12- to 36-h-old full-termpiglets (1.3-2.2 kg) on nasal continuous positive airway pressure (nCPAP) were randomized into four groups: lateral decubitus with right or left side up, prone or supine positions (n = 6 each). All animals received 200 mg kg-1 of poractant alfa mixed with 200 MBq of 99mtechnetium-nanocolloid via a customized eFlow-Neos investigational vibrating-membrane nebulizer. Surfactant deposition (percentage of the administered dose) was measured by gamma scintigraphy. RESULTS: Comparing all groups, the mean total lung surfactant deposition was significantly higher in the prone position (32.4 ± 7.7%, p = 0.03). The deposition in this group was higher in the right lung (21.0 ± 8.6 vs. 11.3 ± 5.7%, p = 0.04). When nebulization was performed in the lateral decubitus, most of the surfactant was found in the dependent lung, regardless of which side the piglet lay on (right side up 15.3 ± 1.0 vs. 3.4 ± 1.0%, p = 0.06, and left side up 11.2 ± 9.8 vs. 1.8 ± 0.7%, p = 0.04). CONCLUSIONS: In spontaneously breathing animals on nCPAP, the prone position yielded the highest lung dose. Higher deposition rates in the dependent lung while on lateral decubitus indicates that deposition was also influenced by gravity.

Lung deposition of nebulized surfactant in newborn piglets: Nasal CPAP vs Nasal IPPV.

BACKGROUND: Nasal continuous positive airway pressure support (nCPAP) is the standard of care for prematurely born infants at risk of neonatal respiratory distress syndrome (nRDS). However, nasal intermittent positive pressure ventilation (NIPPV) may be an alternative to nCPAP in babies requiring surfactant, and in conjunction with surfactant nebulization, it could theoretically reduce the need for invasive mechanical ventilation. We compared lung deposition of nebulized poractant in newborn piglets supported by nCPAP or NIPPV. METHODS: Twenty-five sedated newborn piglets (1.2-2.2 kg) received either nCPAP (3 cmH2 O, n = 12) or NIPPV (3 cmH2 O positive end expiratory pressure+3 cmH2 O inspiratory pressure, n = 13) via custom-made nasal prongs (FiO2 0.4, Servo-i ventilator). Piglets received 200 mg kg-1 of technetium-99m-surfactant mixture continuously nebulized with a customized eFlow-Neos investigational vibrating-membrane nebulizer system. Blood gases were taken immediately before, during, and after nebulization. The deposition was estimated by gamma scintigraphy. RESULTS: Mean surfactant deposition in the lungs was 15.9 ± 11.9% [8.3, 23.5] (mean ± SD [95% CI]) in the nCPAP group and 21.6 ± 10% [15.6, 27.6] in the NIPPV group (P = .20). Respiratory rates were similar in both groups. Minute volume was 489 ± 203 [360, 617] in the nCPAP group and 780 ± 239 [636, 924] mL kg-1 min-1 in the NIPPV group (P = .009). Blood gases were comparable in both groups. CONCLUSION: Irrespective of the noninvasive ventilatory support mode used, relatively high lung deposition rates of surfactant were achieved with nebulization. The amounts of deposited surfactant might suffice to elicit a pulmonary function improvement in the context of nRDS.

A novel delivery system for supraglottic atomization allows increased lung deposition rates of pulmonary surfactant in newborn piglets.

BACKGROUND: Earlier attempts to deliver effective lung doses of surfactant by aerosolization were unsuccessful, mostly because of technical shortcomings. We aimed at quantifying the lung deposition of poractant alfa with a new supraglottic delivery system for surfactant atomization in an experimental neonatal model. METHODS: The method involved six sedated 1-day-old piglets lying in the lateral decubitus, spontaneously breathing on nasal-mask continuous positive airway pressure (nCPAP). A pharyngeal cannula housing a multi-channel air-blasting atomization catheter was placed through the mouth with its tip above the glottis entrance. In all, 200 mg kg-1 of a 99mTc-surfactant mixture was atomized through the catheter synchronously with inspiration. Six intubated control piglets received an equal amount of intratracheally instilled 99mTc-surfactant mixture. The percentage of the 99mTc-surfactant mixture deposited in the lungs was estimated by scintigraphy. RESULTS: Median (range) deposition in the lungs was 40% (24-68%) after atomization and 87% (55-95%) after instillation (p < 0.001). Overall, almost 80% of the deposited surfactant was in the dependent lung. Effective atomization time (atomizer on) was 28 (17-52) min, yielding an output rate of 0.1-0.2 mL min-1. CONCLUSIONS: Without endotracheal intubation, in spontaneously breathing newborn piglets, this new supraglottic atomizer delivery system attained a median lung deposition of 40% of the nominal dose of surfactant.

Research protocol for mechanical complications after central venous catheterisation: a prospective controlled multicentre observational study to determine incidence and risk factors of mechanical complications within 24 hours after cannulation.

INTRODUCTION: Central venous catheterisation is a common procedure in intensive care therapy and the use of central venous catheters is essential for treatment of many medical disorders. Although rare, central venous catheterisation is associated with mechanical complications that can be life-threatening if untreated. Real-time ultrasound guidance reduces the incidence of mechanical complications when compared with the anatomic landmark method. The purpose of this study is to determine the incidence of and potential risk factors associated with early mechanical complications of central venous catheterisation in an era where real-time ultrasound guidance has become clinical practice. METHODS AND ANALYSIS: This is a prospective, controlled, multicentre, observational study. All participating hospitals follow the same clinical guidelines for central venous catheterisation. Each central venous catheter insertion will be recorded in the common electronic chart system according to a recently revised template. An automated script-based search will identify all recorded central venous catheter insertion templates during the study period and relevant variables will be extracted. Outcome measures and independent variables are pre-defined in this study protocol. Multivariable and univariable logistic regression analysis will be used to determine associations and risk factors of mechanical complications. ETHICS AND DISSEMINATION: The Regional Ethical Review Board in Lund, Sweden has approved this study. The results will be submitted for publication in peer-reviewed medical journals and presented at national and international scientific meetings. TRIAL REGISTRATION NUMBER: NCT03782324.

One oxygen breath shortened the time to return of spontaneous circulation in severely asphyxiated piglets.

AIM: Asphyxiated neonates should be resuscitated with air, but it remains unclear if oxygen supplementation is needed in ineffectively ventilated newborn infants. We studied the return of spontaneous circulation (ROSC) with oxygen or air in an experimental model of inadequate ventilation. METHODS: Asphyxia was induced in 16 newborn piglets until their heart rate was <60 bpm or mean arterial pressure (MAP) <30 mmHg. During the first 10 minutes of resuscitation, they received one breath per minute of oxygen (n = 8) or air (n = 8). Tidal volume was 7.5 mL/kg. If MAP was <30 mmHg for 15 seconds, closed-chest cardiac massage (CCCM) was performed for 45 seconds. From 10 minutes onward, all piglets received normal ventilation with air. ROSC was defined as a heart rate >150 bpm, MAP >40 mmHg and no subsequent CCCM. RESULTS: Before resuscitation, the median arterial pH was 6.73. At 10 minutes, no piglets in the oxygen group needed CCCM, while all did in the air group (p < 0.001). The median time to ROSC was 60 seconds with oxygen and 845 seconds with air (p < 0.001). No brain tissue hyperoxia occurred. CONCLUSION: When ventilation was inadequate, one oxygen breath reduced time to ROSC in piglets with severe metabolic and respiratory acidosis.

Lung deposition of nebulized surfactant in newborn piglets.

BACKGROUND: It would be advantageous for the treatment of neonatal respiratory distress syndrome if effective amounts of surfactant could be delivered by nebulization. OBJECTIVE: To investigate lung deposition and distribution of nebulized porcine surfactant using an investigational eFlow neonatal nebulizer. METHODS: While lying on one side, 1-day-old piglets inhaled 200 mg·kg(-1) of nebulized surfactant via mask, nasal prongs, or tracheal tube. The surfactant was diluted with normal saline to 40 mg·ml(-1) and labeled with (99m)technetium-labelled nanocolloid. Undiluted surfactant (80 mg·ml(-1)) was instilled tracheally in a fourth group. Each group had 8 animals. Lung deposition was measured by gamma scintigraphy, and deposition values were presented as a percentage of the nebulized or instilled dose. RESULTS: The median lung deposition of inhaled surfactant was 5% (range 3-16) via mask, 14% (2-40) via prongs, and 45% (25-56) via tracheal tube (p < 0.05). It was 88% (71-96) with instillation. In all groups, the surfactant preferentially went to the dependent lung. Deposition ratios (upper lung/both lungs) were 0.32 (0.13-0.58), 0.15 (0.05-0.58), 0.16 (0.11-0.23), and 0.08 (0.03-0.46). CONCLUSIONS: Using this nebulizer, the lung depositions of porcine surfactant were 45% via endotracheal tube and 14% via nasal-continuous positive airway pressure (prongs). These figures might be physiologically relevant, but still have to be confirmed in efficacy studies.

Early adrenaline administration does not improve circulatory recovery during resuscitation from severe asphyxia in newborn piglets.

AIM OF THE STUDY: To investigate the effects of early intravenous adrenaline administration on circulatory recovery, cerebral reoxygenation, and plasma catecholamine concentrations, after severe asphyxia-induced bradycardia and hypotension. METHODS: One-day-old piglets were left in apnoea until heart rate and mean arterial pressure were less than 50 min(-1) and 25 mmHg, respectively. They randomly received adrenaline, 10 µgkg(-1) (n=16) or placebo (n=15) and were resuscitated with air ventilation and, when needed, closed-chest cardiac massage (CCCM). Eight not asphyxiated animals served as time controls. RESULTS: CCCM was required in 13 piglets given adrenaline and in 13 given placebo. Time to return of spontaneous circulation was: 72 (66-85)s vs. 77 (64-178)s [median (quartile range)] (p=0.35). Time until cerebral regional oxygen saturation (CrSO(2)) had increased to 30% was 86 (79-152)s vs. 126 (88-309)s (p=0.30). The two groups did not differ significantly in CrSO(2), heart rate, arterial pressure, right common carotid artery blood flow, or number of survivors: 13 vs. 11 animals. Plasma concentration of adrenaline, 2.5 min after resuming ventilation, was 498 (268-868)nmoll(-1) vs. 114 (80-306)nmoll(-1) (p=0.01). Corresponding noradrenaline concentrations were 1799 (1058-4182)nmoll(-1)vs. 1385 (696-3118)nmoll(-1) (ns). In the time controls, the concentrations were 0.4 (0.2-0.6)nmoll(-1) of adrenaline and 1.8 (1.3-2.4)nmoll(-1) of noradrenaline. CONCLUSION: The high endogenous catecholamine levels, especially those of noradrenaline, may explain why early administered adrenaline did not significantly improve resuscitation outcome.