Bedside placement of ventricular access devices under local anaesthesia in neonates with posthaemorrhagic hydrocephalus: preliminary experience.

PURPOSE: Posthaemorrhagic ventricular dilatation in preterm infants is primarily treated using temporising measures, of which the placement of a ventricular access device (VAD) is one option. Permanent shunt dependency rates are high, though vary widely. In order to improve the treatment burden and lower shunt dependency rates, we implemented several changes over the years. One of these changes involves the setting of the surgery from general anaesthesia in the OR to local anaesthesia in bed at the neonatal intensive care unit (NICU), which may seem counterintuitive to many. In this article, we describe our surgical technique and present the results of this regimen and compare it to our previous techniques. METHODS: Retrospective study of a consecutive series of 37 neonates with posthaemorrhagic ventricular dilatation (PHVD) treated using a VAD, with a cohort I (n = 13) treated from 2004 to 2008 under general anaesthesia in the OR, cohort II (n = 11) treated from 2009 to 2013 under general anaesthesia in the NICU and cohort III (n = 13) treated from December 2013 to December 2017 under local anaesthesia on the NICU. RESULTS: The overall infection rate was 14%; the VAD revision rate was 22% and did not differ significantly between the cohorts. Procedures under local anaesthesia never required conversion to general anaesthesia and were well tolerated. After an average of 33 tapping days, 38% of the neonates received a permanent ventriculoperitoneal (VP) shunt. The permanent VP shunt rate was 9% with VAD placement under local anaesthesia and 52% when performed under general anaesthesia (p = 0.02). CONCLUSION: Bedside placement of VADs for PHVD under local anaesthesia in neonates is a low-risk, well-tolerated procedure that results in at least equal results to surgery performed under general anaesthesia and/or performed in an OR.

NEOnatal Central-venous Line Observational study on Thrombosis (NEOCLOT): evaluation of a national guideline on management of neonatal catheter-related venous thrombosis.

BACKGROUND: In critically ill (preterm) neonates, catheter-related venous thromboembolism (CVTE) can be a life-threatening complication. Evidence on optimal management in the literature is lacking. In the Netherlands, a consensus-based national management guideline was developed to create uniform CVTE management. OBJECTIVES: To evaluate the efficacy and safety of the national guideline. METHODS: This prospective, multicenter, observational study included all infants aged ≤6 months with CVTE in the Netherlands between 2014 and 2019. CVTE was divided into thrombosis in veins and that in the right atrium, with their own treatment algorithms. The primary outcomes were recurrent venous thrombotic events (VTEs) and/or death due to CVTE as well as major bleeding. RESULTS: Overall, 115 neonates were included (62% male; 79% preterm). The estimated incidence of CVTE was 4.0 per 1000 neonatal intensive care unit admissions. Recurrent thrombosis occurred in 2 (1.7%) infants and death due to CVTE in 1 (0.9%) infant. Major bleeding developed in 9 (7.8%) infants: 2 of 7 (29%) on recombinant tissue plasminogen activator, which was given for high-risk right-atrium thrombosis, and 7 of 63 (11%) on low-molecular-weight heparin (LMWH). Five of the 7 bleedings because of LMWH were complications of subcutaneous catheter use for LMWH administration. CONCLUSION: The management of neonatal CVTE according to the Dutch CVTE management guideline led to a low incidence of recurrent VTEs and death due to VTEs. Major bleeding occurred in 7.8% of the infants. Specific guideline adjustments may improve efficacy and, especially, safety of CVTE management in neonates.

Surveillance study of apparent life-threatening events (ALTE) in the Netherlands.

SIDS and ALTE are different entities that somehow show some similarities. Both constitute heterogeneous conditions. The Netherlands is a low-incidence country for SIDS. To study whether the same would hold for ALTE, we studied the incidence, etiology, and current treatment of ALTE in The Netherlands. Using the Dutch Pediatric Surveillance Unit, pediatricians working in second- and third-level hospitals in the Netherlands were asked to report any case of ALTE presented in their hospital from January 2002 to January 2003. A questionnaire was subsequently sent to collect personal data, data on pregnancy and birth, condition preceding the incident, the incident itself, condition after the incident, investigations performed, monitoring or treatment initiated during admission, any diagnosis made at discharge, and treatment or parental support offered after discharge. A total of 115 cases of ALTE were reported, of which 110 questionnaires were filled in and returned (response rate 97%). Based on the national birth rate of 200,000, the incidence of ALTE amounted 0.58/1,000 live born infants. No deaths occurred. Clinical diagnoses could be assessed in 58.2%. Most frequent diagnoses were (percentages of the total of 110 cases) gastro-esophageal reflux and respiratory tract infection (37.3% and 8.2%, respectively); main symptoms were change of color and muscle tone, choking, and gagging. The differences in diagnoses are heterogeneous. In 34%, parents shook their infants, which is alarmingly high. Pre- and postmature infants were overrepresented in this survey (29.5% and 8.2%, respectively). Ten percent had recurrent ALTE. In total, 15.5% of the infants were discharged with a home monitor. In conclusion, ALTE has a low incidence in second- and third-level hospitals in the Netherlands. Parents should be systematically informed about the possible devastating effects of shaking an infant. Careful history taking and targeted additional investigations are of utmost importance.

Application of ultrasound dilution technology for cardiac output measurement: Cerebral and systemic hemodynamic consequences in a juvenile animal model.

OBJECTIVE: Analysis of cerebral and systemic hemodynamic consequences of ultrasound dilution cardiac output measurements. DESIGN: : Prospective, experimental piglet study. SETTING: Animal laboratory. SUBJECTS: Nine piglets. INTERVENTIONS: Ultrasound dilution cardiac output measurements were performed in ventilated, anesthetized piglets. Interventions that are required for ultrasound dilution cardiac output measurement were evaluated for its effect on cerebral and systemic circulation and oxygenation. MEASUREMENTS AND MAIN RESULTS: DeltacHbD and DeltactHb, representing changes in cerebral blood flow and cerebral blood volume, respectively, were measured with near infrared spectrophotometry. Pulmonary artery (Q) and left carotid artery (Q) blood flow were assessed with transit time flow probes. Starting and/or stopping blood flowing through the arteriovenous loop did not cause relevant hemodynamic changes. Fast injection of isotonic saline caused a biphasic change in DeltacHbD and DeltactHb. After injection of 0.5 mL/kg, the mean (sd) increase in DeltacHbD and DeltactHb was 0.175 (0.213) micromol/L and 0.122 (0.148) micromol/L, respectively, with a subsequent mean decrease of -0.191 (0.299) micromol/L and -0.312 (0.266) micromol/L. Injection of 1.0 mL/kg caused a mean increase in DeltacHbD and DeltactHb of 0.237 (0.203) micromol/L and 0.179 (0.162) followed by a mean decrease of -0.334 (0.407) micromol/L and -0.523 (0.335) micromol/L, respectively. Q and Q changed shortly with a mean increase of 5.9 (3.0) mL/kg/min and 0.23 (0.10) mL/kg/min after injection of 0.5 mL/kg and with 12.0 (4.2) mL/kg/min and 0.44 (0.18) mL/kg/min after injection of 1.0 mL/kg, respectively. The observed changes were more profound after an injection volume of 1.0 mL/kg compared with 0.5 mL/kg for DeltacHbD (p = .06), DeltactHb (p = .09), Q, and Q (p < .01). No relevant changes in mean arterial blood pressure or heart rate were detected in response to the indicator injection. CONCLUSIONS: Cardiac output measurement by ultrasound dilution does not cause clinically relevant changes in cerebral and systemic circulation and oxygenation in a piglet model.

Effects of skin on bias and reproducibility of near-infrared spectroscopy measurement of cerebral oxygenation changes in porcine brain.

The influence of skin on the bias and reproducibility of regional cerebral oxygenation measurements is investigated using cw near-infrared spectroscopy (NIRS). Receiving optodes are placed over the left and right hemispheres of a piglet (C3, C4 EEG placement code) and one transmitting optode centrally (Cz position). Optical densities (OD) are measured during stable normo, mild, and deep hypoxemia. This is done for skin condition 1: all optodes on the skin; skin condition 2: transmitting optode on the skin and one receiving optode on the skull; and skin condition 3: all optodes on the skull. Absolute changes of oxy- (cO2Hb), deoxyhemoglobin (cHHb), and total hemoglobin (ctHb) concentrations [micromolL] are calculated from the ODs. These absolute changes are calculated for each skin condition with respect to normoxic condition. Additionally, for skin condition 2, the difference of concentration changes between receiver 1 (skull) and receiver 2 (skin) is calculated. The effect of skin removal is an average increase of attenuation changes by a factor of 1.66 (=0.51 OD) and of the concentration changes due to the arterial oxygen saturation steps by 23%. We conclude that skin significantly influences regional oxygenation measurements. Nevertheless, it is hypothesized that the estimated concentration changes are dominated by changes of the oxygenation in the brain.

Influence of volume replacement with colloids versus crystalloids in neonates on venoarterial extracorporeal membrane oxygenation on fluid retention, fluid balance, and ECMO runtime.

In this retrospective study, we compared the effects of colloid versus crystalloid fluid replacement on the clinical signs of capillary leakage syndrome in 30 neonates with pulmonary hypertension due to meconium aspiration syndrome on venoarterial membrane oxygenation (VA-ECMO). Before 2000, 15 neonates received volume replacement with a pasteurized plasma protein solution (3.8% albumin); after 2000, 15 neonates received normal saline. Patient characteristics and pre-ECMO values did not differ between the two groups. Total fluid balance was also equal. Diuretic use was significantly higher in the colloid group (p < 0.001). The chest wall soft-tissue index was significantly higher in the crystalloid group (p < 0.005), as were the ventilator settings at the end of the ECMO runtime (p < 0.05). Serum colloid osmotic pressure, albumin, urea nitrogen, and creatinine were significantly higher in the colloid group (p < 0.0001, < 0.0001, < 0.001, and < 0.05, respectively). Duration of VA-ECMO, of artificial ventilation after ECMO treatment, and the mortality rate did not differ between the two groups. We conclude that volume replacement with crystalloids in neonates on VA-ECMO aggravated the edema in a preexisting situation of capillary leakage syndrome, whereas volume replacement with colloids could impair the kidney function.

Ductus arteriosus with left-to-right shunt during venoarterial extracorporeal membrane oxygenation: effects on cerebral oxygenation and hemodynamics.

OBJECTIVE: To investigate the effect on cerebral oxygenation and hemodynamics of a patent ductus arteriosus with left-to-right shunt during venoarterial extracorporeal membrane oxygenation in a lamb model. DESIGN: Prospective intervention study in animals. SETTING: Animal research laboratory of a university medical center. SUBJECTS: Six anesthetized newborn lambs with patent ductus arteriosus and left-to-right shunt, installed on venoarterial extracorporeal membrane oxygenation. INTERVENTIONS: Six lambs of 140 days gestational age were prepared to keep the ductus arteriosus open by infiltration of the vessel wall with formaline 10%. The animals were installed on standard venoarterial extracorporeal membrane oxygenation. With a mechanical occluder, the ductus was closed. MEASUREMENTS AND MAIN RESULTS: Changes of mean arterial blood pressure and carotid artery blood flow were measured simultaneously. Using near infrared spectrophotometry, we calculated changes in cerebral concentration of oxyhemoglobin and deoxyhemoglobin (reflecting changes in cerebral oxygen supply) and total hemoglobin (reflecting changes in cerebral blood volume). Also, cerebral oxygen delivery before and after ductus closure was calculated. Before ductus closure there was a left-to-right shunt with a mean +/- SEM of 41 +/- 20% of total body blood flow. Closure of the ductus resulted in an immediate increase in mean arterial blood pressure and carotid artery blood flow. The concentration of oxyhemoglobin increased and the concentration of deoxyhemoglobin decreased, representing increased cerebral oxygen supply. The concentration of total hemoglobin was unchanged, representing unchanged cerebral blood volume. There was an increase in cerebral oxygen delivery. CONCLUSIONS: In this lamb model, a considerable left-to-right shunt over the ductus during venoarterial extracorporeal membrane oxygenation reduced cerebral circulation and oxygenation.

Monitoring of cerebral haemodynamics in newborn infants.

The most important cerebrovascular injuries in newborn infants, particularly in preterm infants, are cerebral haemorrhage and ischemic injury. The typical cerebral vascular anatomy and the disturbance of cerebral haemodynamics play important roles in the pathophysiology. The term 'cerebral haemodynamics' includes cerebral blood flow (CBF), cerebral blood flow velocity, and cerebral blood volume (CBV). Therapy aimed at changing vascular anatomy is not available. Therefore, prevention of disturbances in CBF and CBV is pivotal. However, continuous monitoring of CBF and CBV is still unavailable for clinical use. Tissue oxygenation may be used as a surrogate for CBF, although precision is still questionable. General knowledge of the regulation of CBF and CBV is important. Although this knowledge is still incomplete, especially regarding autoregulation and the exact role of CBV, it is still useful. Using it even without knowing the exact level of CBF and CBV, it is possible to aim to keep CBF and CBV stable. Future research should focus on development of monitoring tools, gaining more insight in neonatal cerebral autoregulation, and demonstrating clinical benefits of a 'cerebral perfusion-oriented' therapy.

Cardiac output measurement in ventilated lambs with a significant left-to-right shunt using the modified carbon dioxide fick method.

BACKGROUND: It remains a great challenge to measure systemic blood flow in critically ill newborns. In a former study we validated the modified carbon dioxide Fick (mCO(2)F) method for measurement of cardiac output in a newborn lamb model. In this new study we studied the influence of a left-to-right shunt on the accuracy of the mCO(2)F method. OBJECTIVE: To analyze the influence of a left-to-right shunt on the agreement between cardiac output measurement with the mCO(2)F method and ultrasonic transit time pulmonary blood flow in a lamb model. METHODS: The study was approved by the Ethical Committee on Animal Research of the Radboud University Nijmegen and performed in 8 random-bred lambs. A Gore-Tex shunt was placed between the left pulmonary artery and the descending aorta. This aortopulmonary shunt was intermittently opened and closed, while cardiac output was manipulated by creating hemorrhagic hypotension. Cardiac output measurement with the mCO(2)F method (Q(mCO2F)) was compared with pulmonary blood flow obtained by a transit time ultrasonic flow probe positioned around the common pulmonary artery (Q(APC)). RESULTS: Bias, defined as Q(mCO2F) - Q(APC), was calculated for each measurement. With an open shunt there was a significant left-to-right shunt (mean Qp/Qs ratio 2.26; range 1.56-3.69). Mean bias (SD) was -12.3 (50.4) ml x kg(-1) x min(-1) and -12.3 (42.7) ml x kg(-1) x min(-1) for measurements with a closed and open shunt, respectively (no statistical significant difference). CONCLUSIONS: Cardiac output measurement with the mCO(2)F method is reliable and easily applicable in ventilated newborn lambs, also in the presence of a significant left-to-right shunt.

Cardiac output measurement using a modified carbon dioxide Fick method: a validation study in ventilated lambs.

Cardiac output can be measured using a modified carbon dioxide Fick (mCO2F) method. A validation study was performed comparing mCO2F method-derived cardiac output (Q(mCO2F)) with invasively measured pulmonary blood flow. In seven randomly bred ventilated newborn lambs, cardiac output was manipulated by creating hemorrhagic hypotension. When steady state was reached, Q(mCO2F) was measured. Gas analysis was performed in simultaneously obtained arterial and venous blood samples (right atrium [RA], superior vena cava [SVC], and inferior vena cava [IVC]). Carbon dioxide exchange and pulmonary blood flow was measured continuously using a CO2SMO Plus monitor and a pulmonary ultrasonic flow probe (Q), respectively. Mean bias, defined as Q(mCO2F) - Q(ufp), was small (respectively, -0.082 L.min, -0.085 Lx min(-1) and -0.183 Lxmin(-1) for venous sampling from RA, SVC, and IVC). The limits of agreement were -0.328 to 0.164 Lxmin(-1) (RA), -0.335 to 0.165 Lxmin(-1) (SVC), and 0.415 to 0.049 Lxmin(-1) (IVC). In conclusion, measurement of cardiac output with the mCO2F method is reliable and easily applicable in ventilated newborn lambs. For clinical use, the site of venous blood sampling is of minor importance.