Increased intracranial pressure in acute bacterial meningitis.

Acute bacterial meningitis (ABM) is associated with increased intracranial pressure (ICP) caused by bacterial invasion and the host response to infection. Antibiotic therapy is a sine qua non, and adjunct dexamethasone decreases mortality. The ICP increase may have a rapid course and death due to herniation is most often seen within the first week. Evidence regarding treatment of increased ICP in ABM is limited; this review summarises observational studies which point towards reduced mortality by applying a structured approach towards normalization of ICP in ABM.

Mucorales-disseminated infection in burn wound.

A previously fit and well man in his 50s was rescued from a burning apartment with Glasgow Coma Scale 3 and admitted to the burn intensive care unit with 18% mixed dermal and full thickness burns and inhalation injury. He received standardised acute burn treatment according to the Emergency Management of Severe Burn guidelines and was found to have acute kidney injury requiring dialysis and cerebral watershed infarcts. The burns were deep especially on the left leg that was deemed unsalvageable and on day 8, he underwent a mid-femoral amputation.A wound swab on day 8 grew mould and with progression of skin necrosis, Mucorales infection was clinically suspected. Microbiological assessment of the swab confirmed Mucorales infection-an invasive fungus with the ability to invade blood vessels leading to vessel thrombosis and tissue necrosis and associated with high mortality. Recommended radical debridement with free cutaneous margins was not possible due to the widespread disease, and the patient was treated conservatively with antifungal therapy and survived.

Impact of a Treatment Guide on Intravenous Fluids in Minimising the Risk of Hospital-Acquired Hyponatraemia in Denmark.

Hypotonic intravenous (IV) fluids are associated with an increased risk of hospital-acquired hyponatraemia, eventually leading to brain injury and death. We evaluated the effectiveness of a treatment guide to improve prescribing practices of IV fluids. We conducted a before-and-after cross-sectional survey among physicians working at Danish emergency departments. The primary outcome was prescribing practices of IV fluids. Participants were asked which IV fluid they would select in four clinical scenarios. We applied multivariate logistic regression models to estimate the odds ratio of selecting hypotonic fluids. Secondary outcomes included knowledge about IV fluids and hyponatraemia, and the receipt, reading, and usefulness of the treatment guide. After the intervention, about a third (47/154) reported that they would use hypotonic fluids in patients with increased intracranial pressure, and a quarter (39/154) would use hypotonic maintenance fluids in children, both of which are against guideline recommendations. A total of 46% selected the correct fluid, a 3% hypertonic saline solution for a patient with hyponatraemia and severe neurological symptoms. None of the knowledge questions met the predefined criteria of success of 80% correct answers. Of the respondents, 22% had received the treatment guide. Since the implementation failed, we recommend improving distribution by applying methods from implementation science.

Haloperidol for the Treatment of Delirium in ICU Patients.

BACKGROUND: Haloperidol is frequently used to treat delirium in patients in the intensive care unit (ICU), but evidence of its effect is limited. METHODS: In this multicenter, blinded, placebo-controlled trial, we randomly assigned adult patients with delirium who had been admitted to the ICU for an acute condition to receive intravenous haloperidol (2.5 mg 3 times daily plus 2.5 mg as needed up to a total maximum daily dose of 20 mg) or placebo. Haloperidol or placebo was administered in the ICU for as long as delirium continued and as needed for recurrences. The primary outcome was the number of days alive and out of the hospital at 90 days after randomization. RESULTS: A total of 1000 patients underwent randomization; 510 were assigned to the haloperidol group and 490 to the placebo group. Among these patients, 987 (98.7%) were included in the final analyses (501 in the haloperidol group and 486 in the placebo group). Primary outcome data were available for 963 patients (97.6%). At 90 days, the mean number of days alive and out of the hospital was 35.8 (95% confidence interval [CI], 32.9 to 38.6) in the haloperidol group and 32.9 (95% CI, 29.9 to 35.8) in the placebo group, with an adjusted mean difference of 2.9 days (95% CI, -1.2 to 7.0) (P = 0.22). Mortality at 90 days was 36.3% in the haloperidol group and 43.3% in the placebo group (adjusted absolute difference, -6.9 percentage points [95% CI, -13.0 to -0.6]). Serious adverse reactions occurred in 11 patients in the haloperidol group and in 9 patients in the placebo group. CONCLUSIONS: Among patients in the ICU with delirium, treatment with haloperidol did not lead to a significantly greater number of days alive and out of the hospital at 90 days than placebo. (Funded by Innovation Fund Denmark and others; AID-ICU ClinicalTrials.gov number, NCT03392376; EudraCT number, 2017-003829-15.).

Restriction of Intravenous Fluid in ICU Patients with Septic Shock.

BACKGROUND: Intravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU). METHODS: In this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization. RESULTS: We enrolled 1554 patients; 770 were assigned to the restrictive-fluid group and 784 to the standard-fluid group. Primary outcome data were available for 1545 patients (99.4%). In the ICU, the restrictive-fluid group received a median of 1798 ml of intravenous fluid (interquartile range, 500 to 4366); the standard-fluid group received a median of 3811 ml (interquartile range, 1861 to 6762). At 90 days, death had occurred in 323 of 764 patients (42.3%) in the restrictive-fluid group, as compared with 329 of 781 patients (42.1%) in the standard-fluid group (adjusted absolute difference, 0.1 percentage points; 95% confidence interval [CI], -4.7 to 4.9; P = 0.96). In the ICU, serious adverse events occurred at least once in 221 of 751 patients (29.4%) in the restrictive-fluid group and in 238 of 772 patients (30.8%) in the standard-fluid group (adjusted absolute difference, -1.7 percentage points; 99% CI, -7.7 to 4.3). At 90 days after randomization, the numbers of days alive without life support and days alive and out of the hospital were similar in the two groups. CONCLUSIONS: Among adult patients with septic shock in the ICU, intravenous fluid restriction did not result in fewer deaths at 90 days than standard intravenous fluid therapy. (Funded by the Novo Nordisk Foundation and others; CLASSIC ClinicalTrials.gov number, NCT03668236.).

A cross-sectional survey of knowledge pertaining to IV fluid therapy and hyponatraemia among nurses working at emergency departments in Denmark.

INTRODUCTION: Inappropriate fluid therapy may induce or worsen existing hyponatraemia with potentially life-threatening consequences. Nurses have an important role in assisting physicians in IV fluid prescribing. However, research is lacking in Denmark about nurses' knowledge pertaining to IV fluid therapy and hyponatraemia. METHODS: An explorative cross-sectional survey was performed among Danish emergency department nurses in Spring 2019. Knowledge about IV fluid therapy was assessed for three common clinical scenarios, and multiple-choice questions were used to measure knowledge about hyponatraemia. RESULTS: 112 nurses responded to all scenario questions corresponding to 6.2% (112/1815) of the total population of nurses working at emergency departments in Denmark. In two of the three scenarios, a minority of nurses (8-10%) inappropriately selected hypotonic fluids. Nearly one third (31%) selected a hypotonic fluid for a patient with meningitis, which is against guideline recommendations. The study revealed limited knowledge about severe symptoms of hyponatraemia, patients at high risk, and hyperglycaemia-induced hyponatraemia. CONCLUSION: In accordance with guideline recommendation, the majority of nurses did not select hypotonic fluids in three clinical scenarios commonly encountered in the emergency department. However, when setting up an educational program, further awareness is needed regarding symptoms of hyponatraemia, high-risk patients, and hyperglycaemia-induced hyponatraemia.

Fatal case of hospital-acquired hypernatraemia in a neonate: lessons learned from a tragic error.

A 3-week-old boy with viral gastroenteritis was by error given 200 mL 1 mmol/mL hypertonic saline intravenously instead of isotonic saline. His plasma sodium concentration (PNa) increased from 136 to 206 mmol/L. Extreme brain shrinkage and universal hypoperfusion despite arterial hypertension resulted. Treatment with glucose infusion induced severe hyperglycaemia. Acute haemodialysis decreased the PNa to 160 mmol/L with an episode of hypoperfusion. The infant developed intractable seizures, severe brain injury on magnetic resonance imaging and died. The most important lesson is to avoid recurrence of this tragic error. The case is unique because a known amount of sodium was given intravenously to a well-monitored infant. Therefore the findings give us valuable data on the effect of fluid shifts on the PNa, the circulation and the brain's response to salt intoxication and the role of dialysis in managing it. The acute salt intoxication increased PNa to a level predicted by the Edelman equation with no evidence of osmotic inactivation of sodium. Treatment with glucose in water caused severe hypervolaemia and hyperglycaemia; the resulting increase in urine volume exacerbated hypernatraemia despite the high urine sodium concentration, because electrolyte-free water clearance was positive. When applying dialysis, caution regarding circulatory instability is imperative and a treatment algorithm is proposed.

Are Further Interventions Needed to Prevent and Manage Hospital-Acquired Hyponatraemia? A Nationwide Cross-Sectional Survey of IV Fluid Prescribing Practices.

BACKGROUND: Hyponatraemia is associated with increased morbidity, increased mortality and is frequently hospital-acquired due to inappropriate administration of hypotonic fluids. Despite several attempts to minimise the risk, knowledge is lacking as to whether inappropriate prescribing practice continues to be a concern. METHODS: A cross-sectional survey was performed in Danish emergency department physicians in spring 2019. Prescribing practices were assessed by means of four clinical scenarios commonly encountered in the emergency department. Thirteen multiple-choice questions were used to measure knowledge. RESULTS: 201 physicians responded corresponding to 55.4% of the total population of physicians working at emergency departments in Denmark. About a quarter reported that they would use hypotonic fluids in patients with increased intracranial pressure and 29.4% would use hypotonic maintenance fluids in children, both of which are against guideline recommendations. Also, 29.4% selected the correct fluid, a 3% hypertonic saline solution, for a patient with hyponatraemia and severe neurological symptoms, which is a medical emergency. Most physicians were unaware of the impact of hypotonic fluids on plasma sodium in acutely ill patients. CONCLUSION: Inappropriate prescribing practices and limited knowledge of a large number of physicians calls for further interventions to minimise the risk of hospital-acquired hyponatraemia.

[Keraunoparalysis after lightning injury with transient ischaemia and paralysis of an extremity].

Keraunoparalysis is a transient paralysis of the extremities, which results from close contact with lightning. In this case report, a 58-year-old man came in close contact with a bolt of lightning. His left foot was pulseless, pale, cold and with absence of capillary refill. His symptoms were initially interpreted as arterial occlusion, and therefore bypass surgery and even amputation were considered. However, his symptoms resolved within hours. Therefore, clinicians must consider keranoparalysis as a differential diagnosis in patients struck by lightning.

[New Nordic guidelines on management of burn injuries].

Denmark has recently entered a collaboration with other Nordic countries to ensure a common strategy in the management of burn mass casualties. The collaboration is based upon the guideline Emergency Management of Severe Burns originating from the Australian and New Zealand Burn Association. The desire to establish a common Nordic strategy has led to a number of changes in the national guidelines for the treatment of burn injuries. The new guidelines recently implemented at the national university hospital of Denmark, Rigshospitalet, are presented in this review.

[Intravenous fluid therapy in children].

The standard practice in paediatric departments in Danish hospitals is to prescribe hypotonic maintenance fluids (sodium content 20-40 mmol/l) for children, who are fasting or have a reduced enteral intake. The past decades have provided strong evidence, that this can lead to hypo-natraemia and subsequent neurologic damage or death. We recommend, that prefabricated isotonic solutions containing 140-154 mmol/l of sodium and 5% glucose, with or without an additional 20 mmol/l of potassium, are available as standard maintenance fluid for children in all Danish hospitals.

The frequently used intraperitoneal hyponatraemia model induces hypovolaemic hyponatraemia with possible model-dependent brain sodium loss.

NEW FINDINGS: What is the central question of this study? The brain response to acute hyponatraemia is usually studied in rodents by intraperitoneal instillation of hypotonic fluids (i.p. model). The i.p. model is described as 'dilutional' and 'syndrome of inappropriate ADH (SIADH)', but the mechanism has not been explored systematically and might affect the brain response. Therefore, in vivo brain and muscle response were studied in pigs. What is the main finding and its importance? The i.p. model induces hypovolaemic hyponatraemia attributable to sodium redistribution, not dilution. A large reduction in brain sodium is observed, probably because of the specific mechanism causing the hyponatraemia. This is not accounted for in current understanding of the brain response to acute hyponatraemia. Hyponatraemia is common clinically, and if it develops rapidly, brain oedema evolves, and severe morbidity and even death may occur. Experimentally, acute hyponatraemia is most frequently studied in small animal models, in which the hyponatraemia is produced by intraperitoneal instillation of hypotonic fluids (i.p. model). This hyponatraemia model is described as 'dilutional' or 'syndrome of inappropriate ADH (SIADH)', but seminal studies contradict this interpretation. To confront this issue, we developed an i.p. model in a large animal (the pig) and studied water and electrolyte responses in brain, muscle, plasma and urine. We hypothesized that hyponatraemia was induced by simple water dilution, with no change in organ sodium content. Moderate hypotonic hyponatraemia was induced by a single i.v. dose of desmopressin and intraperitoneal instillation of 2.5% glucose. All animals were anaesthetized and intensively monitored. In vivo brain and muscle water was determined by magnetic resonance imaging and related to the plasma sodium concentration. Muscle water content increased less than expected as a result of pure dilution, and muscle sodium content decreased significantly (by 28%). Sodium was redistributed to the peritoneal fluid, resulting in a significantly reduced plasma volume. This shows that the i.p. model induces hypovolaemic hyponatraemia and not dilutional/SIADH hyponatraemia. Brain oedema evolved, but brain sodium content decreased significantly (by 21%). To conclude, the i.p. model induces hypovolaemic hyponatraemia attributable to sodium redistribution and not water dilution. The large reduction in brain sodium is probably attributable to the specific mechanism that causes the hyponatraemia. This is not accounted for in the current understanding of the brain response to acute hyponatraemia.

[Prevention of hospital-acquired hyponatremia].

The hospitalized patient is at risk of hyponatraemia caused by reduced electrolyte free water clearance and prescription of hypotonic fluids. Hospital-acquired hyponatraemia is common and associated with increased mortality/morbidity. Hyponatraemia in itself can cause severe cerebral symptoms. Small decreases in P-[Na⁺] in patients with reduced intracranial compliance (e.g. meningitis) can be dangerous. To reduce iatrogenic hyponatraemia the understanding of P-[Na+] is fundamental. Next, meticulously prescription of fluid amount/quality and reevaluation as with any other drug is of paramount importance.

[Hyponatraemia as the cause of severe cerebral symptoms]. / Hyponatriæmi som årsag til svære cerebrale symptomer.

Hyponatraemia with severe symptoms is a medical emergency that warrants swift action. Treatment can be delayed and/or insufficient if a systematic approach fails. We present two cases of severe symptomatic hyponatraemia: 1) Seizures treated with antiepileptics and isotonic saline, which fails to increase the plasma [Na+]/reveal the symptoms and 2) coma treated successfully with infusions of hypertonic saline boluses. Effective treatment is simple and involves management of airway, breathing and circulation together with bolus infusions of hypertonic saline to ensure controllable plasma [Na+] increase.

Clinical review: practical approach to hyponatraemia and hypernatraemia in critically ill patients.

Disturbances in sodium concentration are common in the critically ill patient and associated with increased mortality. The key principle in treatment and prevention is that plasma [Na+] (P-[Na+]) is determined by external water and cation balances. P-[Na+] determines plasma tonicity. An important exception is hyperglycaemia, where P-[Na+] may be reduced despite plasma hypertonicity. The patient is first treated to secure airway, breathing and circulation to diminish secondary organ damage. Symptoms are critical when handling a patient with hyponatraemia. Severe symptoms are treated with 2 ml/kg 3% NaCl bolus infusions irrespective of the supposed duration of hyponatraemia. The goal is to reduce cerebral symptoms. The bolus therapy ensures an immediate and controllable rise in P-[Na+]. A maximum of three boluses are given (increases P-[Na+] about 6 mmol/l). In all patients with hyponatraemia, correction above 10 mmol/l/day must be avoided to reduce the risk of osmotic demyelination. Practical measures for handling a rapid rise in P-[Na+] are discussed. The risk of overcorrection is associated with the mechanisms that cause hyponatraemia. Traditional classifications according to volume status are notoriously difficult to handle in clinical practice. Moreover, multiple combined mechanisms are common. More than one mechanism must therefore be considered for safe and lasting correction. Hypernatraemia is less common than hyponatraemia, but implies that the patient is more ill and has a worse prognosis. A practical approach includes treatment of the underlying diseases and restoration of the distorted water and salt balances. Multiple combined mechanisms are common and must be searched for. Importantly, hypernatraemia is not only a matter of water deficit, and treatment of the critically ill patient with an accumulated fluid balance of 20 litres and corresponding weight gain should not comprise more water, but measures to invoke a negative cation balance. Reduction of hypernatraemia/hypertonicity is critical, but should not exceed 12 mmol/l/day in order to reduce the risk of rebounding brain oedema.

[A practical treatment of hyponatraemia]. / Praktisk tilgang til den hyponatriæmiske patient.

Hyponatraemia with cerebral symptoms is a medical emergency. Prompt management of airway, breathing and circulation together with repeated boluses of 2 ml/kg 3% NaCl constitute a rational treatment. The goal is remission of symptoms. After the initial correction, the main concern is to avoid overcorrection, thus reducing the risk of osmotic demyelination. P-[Na(+)] and diuresis must be measured frequently together with diuresis. Definitive treatment should be directed toward the aetiology.

Regional differences in osmotic behavior in brain during acute hyponatremia: an in vivo MRI-study of brain and skeletal muscle in pigs.

Brain edema is suggested to be the principal mechanism underlying the symptoms in acute hyponatremia. Identification of the mechanisms responsible for global and regional cerebral water homeostasis during hyponatremia is, therefore, of utmost importance. To examine the osmotic behavior of different brain regions and muscles, in vivo-determined water content (WC) was related to plasma sodium concentration ([Na(+)]) and brain/muscle electrolyte content. Acute hyponatremia was induced with desmopressin acetate and infusion of a 2.5% glucose solution in anesthetized pigs. WC in different brain regions and skeletal muscle was estimated in vivo from T(1) maps determined by magnetic resonance imaging (MRI). WC, expressed in gram water per 100 g dry weight, increased significantly in slices of the whole brain [342(SD = 14) to 363(SD = 21)] (6%), thalamus [277(SD = 13) to 311(SD = 24)] (12%) and white matter [219(SD = 7) to 225(SD = 5)] (3%). However, the WC increase in the whole brain and white mater WC was less than expected from perfect osmotic behavior, whereas in the thalamus, the water increase was as expected. Brain sodium content was significantly reduced. Muscle WC changed passively with plasma [Na(+)]. WC determined with deuterium dilution and tissue lyophilzation correlated well with MRI-determined WC. In conclusion, acute hyponatremia induces brain and muscle edema. In the brain as a whole and in the thalamus, regulatory volume decrease (RVD) is unlikely to occur. However, RVD may, in part, explain the observed lower WC in white matter. This may play a potential role in osmotic demyelination.

Edelman's equation is valid in acute hyponatremia in a porcine model: plasma sodium concentration is determined by external balances of water and cations.

Acute hyponatremia is a serious condition, which poses major challenges. Of particular importance is what determines plasma sodium concentration ([Na(+)]). Edelman introduced an explicit model to describe plasma [Na(+)] in a population as [Na(+)] = alpha.(exchangeable Na(+) + exchangeable K(+))/(total body water) - beta. Evidence for the clinical utility of the model in the individual and in acute hyponatremia is sparse. We, therefore, investigated how the measured plasma [Na(+)] could be predicted in a porcine model of hyponatremia. Plasma [Na(+)] was estimated from in vivo-determined balances of water, Na(+), and K(+), according to Edelman's equation. Acute hyponatremia was induced with desmopressin acetate and infusion of a 2.5% glucose solution in anesthetized pigs. During 480 min, plasma [Na(+)] and osmolality were reduced from 136 (SD 2) to 120 mmol/l (SD 3) and from 284 (SD 4) to 252 mosmol/kgH(2)O (SD 5), respectively. The following interpretations were made. First, Edelman's model, which, besides dilution, takes into account Na(+) and K(+), fits plasma [Na(+)] significantly better than dilution alone. Second, a common value of alpha = 1.33 (SD 0.08) and beta = -13.04 mmol/l (SD 7.68) for all pigs explains well the plasma [Na(+)] in the individual animal. Third, measured exchangeable Na(+) and calculated exchangeable Na(+) + K(+) per weight in the pigs are close to Edelman's findings in humans, whereby the methods are cross-validated. In conclusion, plasma [Na(+)] can be explained in the individual animal by external balances, according to Edelman's construct in acute hyponatremia.