Neuro Protection - PANICC

in a postical infant with suspected raised icp

the use of mannitol vs hypertonic saline

emma broomfield

PATIENT

A 6-month-old female infant, brought to ED with a history of jerking movements leading to a febrile convulsion the day before. Mum presenting to ED as the jerking movements had started again. In the department she had an episode of status epilepticus for 35 minutes requiring midazalam, IV Lorazepam and Levetriacetam. Patient was born via spontaneous vaginal delivery at 40 weeks with no complications. Patient has been well since birth. Mum reported male sibling, aged 9, has epilepsy diagnosed at 8 months of age. Weight: 6.7kg

EXPOSURE

DISABILITY

PEWS Score: 6 utilising local PEWS Chart. According to the Paediatric Critical Care Society (2021) guidelines this patient meets the criteria for Level 1 Critical Care, however, it could be argued this patient required higher level critical care due to the need for one to one care, continuous monitoring and the use of hypertonic saline.

AIRWAY

BREATHING

POSTICAL ASSESSMENT

CIRCULATION

A blood gas was taken which was abnormal due to prolonged seizure activity. It showed respiratory acidaemia as the pH is under 7.35 but the pCO2 is over 6kPa. This is likely due to the respiratory depression during the seizure reducing the removal of the increased carbon dioxide produced (Hawkes & Hocker, 2018).The blood gas ruled out electrolyte abnormalities including hyponatremia and hypoglycaemia.

Investigations

The patient was taken to CT due to prolonged seizure activity and abnormal posturing - the CT appeared normal although awaiting formal report.

Some animal studies have shown a fail of these mechanisms around 20-40 minutes into the seizure, however, the evidence supporting this same timeframe in human trials is significantly less (Fernández et al., 2019).This could lead to acidemia, as seen in this patient, or hypogylcaemia, hypoxia and hypotension (Kandel et al., 2021). Hyperthermia was also noted in this patient, which could have been due to repetitive musle contracts as opposed to an infective cause (Fernández et al., 2019).

Kandel et al. (2021) states that any increase in brain tissue, blood, CSF or fluid increases pressure as the capacity within the cranium is fixed. The hypothalamus response increasing blood pressure leads to increased cerebral blood flow, leading to increased ICP (Hawkes & Hocker, 2018).

Seizure activity disrupts brain activity across both hemispheres in a generalised seizure (Kandel et al., 2021). Seizure activity stimulates the hypothalamus stress response, increased blood pressure and glucose to meet increased metabolic demand which was seen in this patient (Kandel et al., 2021).

Pathophysiology of seizures and raised ICP

Due to the links of seizures with raised ICP and the posturing displayed by the patient, raised ICP was assumed, however, this could also have been caused by a hypoxic brain injury, CNS infection or due to the postical state. Due to this, hypertonic saline (2.7%) was administered at 3ml/kg over 15 minutes (Lillie, J., 2022).

It has been shown that raised ICP can cause decerebrate posturing (Knight & Decker, 2023). It is believed that the vestibular nucleus causes decerebrate posturing by activating the extensor motor neurons. When functioning normally, the higher brain centres inhibit this reflex, therefore, decerebrate posturing results when there is a failure of this connection (Knight & Decker, 2023)

Hypertonic saline has an osmotic action. The majority of this movement is from the intracellular space to the intravascular space (Strandvik, G, 2009). Hyperosmolar therapy reduces ICP which in turn increases cerebral perfusion (Strandvik, G., 2009)

Pathophysiology of decerebrate posturing and hypertonic saline

(Albialy, A. et al., 2021)

Mannitol vs 3% hypertonic saline in children with intracranial hypertension: review of the current evidence

This review looked at the improvement of Cerebral Perfusion Pressure (CPP) and reduction in ICP, aswell as mortality, duration of ventilation and length of PICU stay of both medications in both traumatic and non-traumatic causes of raised ICP. 8 studies in total were included:2 randomised control trials (2019 and 2020)4 retrospective studies (1999, 2005, 2013 and 2016)2 systematic reviewsThe review found that hypertonic saline caused a greater improvement in ICP and CPP, as well as being associated with lower mortality and shorter periods of intubation and PICU stays in both traumatic and non-traumatic circumstances. The study did, however, find there was a lack of high-quality evidence to support these findings and recommends larger studies across several centres to base guidelines on.

The study presents a clear question within the title and objectives, however, there is a wide scope of the review including differing aetiologies which may make it difficult to apply the findings to a specific case scenario. The full search criteria and inclusion criteria were not provided, making it difficult to ascertain if any relevant studies were missed. Some of the evidence utilised are dated back to over 10 years ago, The studies included all had similar conculsions regarding the use of hypertonic saline, apart from 1 study in which the researchers discussed the statistical significance of this. The studies used were carried out in other countries including USA, Canada, India and Turkey, and therefore, care should be taken when applying findings to the UK population.

using the Systematic Review crticial appraisal tool by the Centre for Evidence-Based Medicine (2024)

(Albialy, A. et al., 2021)

Mannitol vs 3% hypertonic saline in children with intracranial hypertension: review of the current evidence

Critique of the Review

(Mishra, N. J. et al., 2023)

Hypertonic Saline vs. Mannitol in Management of Elevated Intracranial Pressure in Children: A Meta-Analysis

This review compared the efficacy and safety of Mannitol and Hypertonic Saline. Four randomised control trials were included, which included both traumatic and non-traumatic incidence of raised ICP. The primary outcome in this case was mortality. Interestingly, there was no significant difference in mortality, duration of PICU admission or ventilation, GCS, CPP and ICP. The certainty of all evidence included was very-low to moderate certainty, leading researchers to conclude higher quality data is required to guide any recommendations on medication preference.

(Mishra, N. J. et al., 2023)

Hypertonic Saline vs. Mannitol in Management of Elevated Intracranial Pressure in Children: A Meta-Analysis

The study presents a clear focus for the meta-analysis and defines clearly the primary and secondary outcomes being studied. The researchers utilised several databases including Cochrane, PubMed and Clinical Trials registry, which means it is likely to have included all important and relevant studies. Non-english language articles were not included which does risk some important articles having been excluded during the process. The inclusion criteria was appropriate to the question posed and the exclusion criteria was clearly rationalised. This study utilised the GRADE Profiler software to rate the quality and certainty of evidence reducing bias. Simarly to the previous review, both traumatic and non-traumatic cases were included, which impacts its application to specific circumstances. Further, all trials included were carried out in India which impacts the ability to generalise these results to the UK.

using the Systematic Review crticial appraisal tool by the Centre for Evidence-Based Medicine (2024)

Critique of the Review

When exposed, there were no obvious wounds, rashes or injuries. No sign of a head injury. Patient had 1 IV cannula in her left hand. VIP Score 0.

The patient had a GCS of 8/15. The patient was noted to have some stiffening to limbs but no longer had decerebrate posturing. Blood glucose levels were measured and were 7.8mmol/L. Pupil assessment was undertaken which was unremarkable with pupils being equal and reactive to light. Unable to assess pain due to reduced concious level.

The patient’s heart rate was 112 beats per minute. The patient was hypertensive at 101/71 and her pulse volume was normal. The capillary refill time was two second peripherally and two second centrally, she felt cool peripherally but mottling was settling. The patient’s temperature was 38.3 degrees celsius.

The patient’s respiratory rate was 29 breaths per minute, which whilst low was not unexpected due to medication given and increasing. The patient’s chest was exposed and there were no signs of increased work of breathing. Oxygen saturations were 96% in room air with airway manoeuvres.

Airway at risk due to reduced conciousness. Anaesthetists present but decided not to intubate at this point due to increasing conciousness level. Airway currently being maintained using head tilt.No additional airway sounds.

EXPOSURE

DISABILITY

AIRWAY

BREATHING

ASSESSMENT FOLLOWING HYPERTONIC SALINE

CIRCULATION

During the seizure, initially it was not clear of who was leading the care - however, a peri-arrest was placed quickly ensuring the correct skill mix was achieved quickly. During the review, it was noted that a full history was not taken as the patient was not seen by the medical team prior to the seizure. Whilst a member of the team was allocated to supporting mum, it would have been beneficial if this was a member of the medical team to ensure a full history was taken, optimising care. Whilst reviewing this case study, it has been difficult to draw definitive conclusions due to the nature of ED, where only a snapshot of the patients condition and journey is captured. Furthermore, often feedback is not recieved following a patient leaving our department and not fed back to the team involved in the clinical care. To improve learning from clinical cases, it would be beneficial to have a robust process in place for following up on these cases to inform future practice. I acknowledge that this case is extremely complex which leads to further difficulty when applying findings to future cases.

RECOMMENDATIONS FOR PRACTICE

The research I have carried out has shown a lack of high-quality research and data on the use of hypertonic saline in raised ICP. Specifically, alot of the research found was relating to traumatic brain injuries which does not apply in this case study. It would be beneficial for a multi-centre trial to be carried out within the UK to provide certainty in the best treatment for raised ICP within our care setting. Going forward whilst awaiting higher quality evidence, I would recommend the use of hypertonic saline as some research studies have concluded hypertonic saline is more beneficial for the paediatric population and the patient in this case study's condition improved following the administration of hypertonic saline. This falls in line with the current Paediatric Emergencies guidelines and STRS guidelines (Lillie, J., 2022)

RECOMMENDATIONS FOR PRACTICE

strandvik, g.f. (2009). Hypertonic saline in critical care: a review of the literature and guidelines for use in hypotensive states and raised intracranial pressure. association of anaesthetists. https://doi.org/10.1111/j.1365-2044.2009.05986.x

albialy, a., sherif, a., orazulume, c. & mehrez, m. (2021). 785 mannitol vs 3% hypertonic saline in children with intracranial hypertension: review of the current evidence. archives of disease in childhood. 106, A113-A114

Fernández, i.s., goodkin, h.p. & scott, r.c. (2019). pathophysiology of convulsive status epilepticus. seizure: european journal of epilepsy, 68, 16-21.

Rameshkumar, R., Bansal, A., Singhi, S., Singhi, P. and Jayashree, M. (2020) Randomized Clinical Trial of 20% Mannitol Versus 3% Hypertonic Saline in Children With Raised Intracranial Pressure Due to Acute CNS Infections. Paediatric Critical care medicine. 21 (12). 1071-1080.

lillie, j. (2022). Paediatric Critical Care: Time Critical Neurosurgical Transfer. https://www.evelinalondon.nhs.uk/resources/our-services/hospital/south-thames-retrieval-service/neurosurgical-transfer-mar-2018.pdf.

knight, j & decker, l.c. (2023, july 31). Decerebrate and Decorticate Posturing. national library of medicine. https://www.ncbi.nlm.nih.gov/books/NBK559135/

Centre for evidence-based medicine (2024). systematic review crticial appraisal sheet. https://www.cebm.ox.ac.uk/files/ebm-tools/systematic-review.pdf.

kandel. E.R., koester, j.d., mack, s.h. & siegelbaum, s.a. (2021) principles of neural science (6th ed.) mcgraw-hill education.

Hawkes, M.A.,& Hocker, S.E. (2018) Systemic Complications Following Status Epilepticus. Current Neurology and Neuroscience Reports, 18 (7), https://doi.org/10.1007/s11910-018-0815-9

National Institute for Health and Care Excellence, (n.d.). BNF For Children - midazolam. https://bnfc.nice.org.uk/drugs/midazolam/

References

Paediatric Critical Care Society. (2021). Quality Standards for the Care of Critically Ill or Injured Children. 6th Edition. https://pccsociety.uk/wp-content/uploads/2021/10/PCCS-Standards-2021.pdf.

When exposed, there were no obvious wounds, rashes or injuries. No sign of a head injury. Patient had 1 IV cannula in her left hand. VIP Score 0.

EXPOSURE

When exposed, there were no obvious wounds, rashes or injuries. No sign of a head injury. Patient had 1 IV cannula in her left hand. The site looked clean and dry with no redness or swelling present.

EXPOSURE

Airway at risk due to reduced conciousness. Anaesthetists present but decided not to intubate at this point.Airway currently being maintained using head tilt and jaw thrust manoeurves - there was also increased secretions which required suctioning.No additional airway sounds.

AIRWAY

Airway at risk due to reduced conciousness. Anaesthetists present but decided not to intubate at this point due to increasing conciousness level. Airway currently being maintained using head tilt.No additional airway sounds.

AIRWAY

The patient’s respiratory rate was 29 breaths per minute, which whilst low was not unexpected due to medication given and increasing. The patient’s chest was exposed and there were no signs of increased work of breathing. Oxygen saturations were 96% in room air with airway manoeuvres.

BREATHING

The patient had a GCS of 8/15. The patient was noted to have some stiffening to limbs but no longer had decerebrate posturing. Blood glucose levels were measured and were 7.8mmol/L. Pupil assessment was undertaken which was unremarkable with pupils being equal and reactive to light. Unable to assess pain due to reduced concious level.

DISABILITY

The patient’s heart rate was 112 beats per minute. The patient was hypertensive at 101/71 and her pulse volume was normal. The capillary refill time was two second peripherally and two second centrally, she felt cool peripherally but mottling was settling. The patient’s temperature was 38.3 degrees celsius.

CIRCULATION

The patient’s heart rate was 102 beats per minute. The patient was hypertensive at 131/64, however, this was considered expected due to the seizure and her pulse volume was normal. The capillary refill time was three second peripherally and two second centrally, she felt cool peripherally with mottling. The patient’s temperature was 39.9 degrees celsius. The patient had already had paracetamol.

CIRCULATION

The patient is unresponsive with GCS of 4/15. The patient was noted to have decerebrate posturing. Blood glucose levels were measured and were 8.4mmol/L., pupil assessment was undertaken which was unremarkable with pupils being equal and reactive to light. Unable to assess pain due to reduced concious level.

DISABILITY

The patient’s respiratory rate was 23 breaths per minute, which whilst low was not unexpected due to medication given. The patient’s chest was exposed and there were no signs of increased work of breathing. Oxygen saturations were 98% in 100% 02 via a non-rebreathing mask.

BREATHING