Acute Central Diabetes Insipidus Research Articles

Cannabinoid receptor type 1 activation causes a water diuresis by inducing an acute central diabetes insipidus in mice.

Cannabis and synthetic cannabinoid consumption are increasing worldwide. Cannabis contains numerous phytocannabinoids that act on the G protein-coupled cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 expressed throughout the body, including the kidney. Essentially every organ, including the kidney, produces endocannabinoids, which are endogenous ligands to these receptors. Cannabinoids acutely increase urine output in rodents and humans, thus potentially influencing total body water and electrolyte homeostasis. As the kidney collecting duct (CD) regulates total body water, acid/base, and electrolyte balance through specific functions of principal cells (PCs) and intercalated cells (ICs), we examined the cell-specific immunolocalization of CB1R in the mouse CD. Antibodies against either the C-terminus or N-terminus of CB1R consistently labeled aquaporin 2 (AQP2)-negative cells in the cortical and medullary CD and thus presumably ICs. Given the well-established role of ICs in urinary acidification, we used a clearance approach in mice that were acid loaded with 280 mM NH4Cl for 7 days and nonacid-loaded mice treated with the cannabinoid receptor agonist WIN55,212-2 (WIN) or a vehicle control. Although WIN had no effect on urinary acidification, these WIN-treated mice had less apical + subapical AQP2 expression in PCs compared with controls and developed acute diabetes insipidus associated with the excretion of large volumes of dilute urine. Mice maximally concentrated their urine when WIN and 1-desamino-8-d-arginine vasopressin [desmopressin (DDAVP)] were coadministered, consistent with central rather than nephrogenic diabetes insipidus. Although ICs express CB1R, the physiological role of CB1R in this cell type remains to be determined.NEW & NOTEWORTHY The CB1R agonist WIN55,212-2 induces central diabetes insipidus in mice. This research integrates existing knowledge regarding the diuretic effects of cannabinoids and the influence of CB1R on vasopressin secretion while adding new mechanistic insights about total body water homeostasis. Our findings provide a deeper understanding about the potential clinical impact of cannabinoids on human physiology and may help identify targets for novel therapeutics to treat water and electrolyte disorders such as hyponatremia and volume overload.

FRI350 Prolonged Transient Central Diabetes Insipidus Induced By Traumatic Brain Injury

Abstract Disclosure: R. Marques: None. S. Sharma: None. B.S. Flores Chang: None. A. Sajan: None. Introduction: Central diabetes insipidus (CDI) is a rare complication of traumatic brain injury (TBI). Most cases of CDI due to TBI are transient and resolve within 2-5 days. We report a patient with prolonged transient CDI which lasted for 35 days after sustaining a gunshot wound to the head. Case Description: A 17-year-old male with no past medical history presented after gunshot wound in the head. He had comminuted fractures of the right temporal bone, right zygomatic arch, greater and lesser rings of sphenoid bone, right maxillary sinus, right medial orbital wall, right orbital floor and bilateral frontal sinuses. A computerized tomography of head showed subarachnoid haemorrhage of the frontal lobes as well as subdural haemorrhage of right parietal lobe, right falx cerebri and left cerebral hemisphere. On hospital day 2, he had an intracranial pressure monitor placed which was unremarkable. He underwent right hemicraniectomy with debridement and washout on hospital day 3. Shortly afterwards, his urine output increased to >500 cc/hr with serum sodium of 172 mEq/L [135-145], serum osmolality 307 mOsmol/kg [270-295], and urine osmolality of 117 mOsm/kg [300-900]; consistent with CDI. He was acutely treated with intravenous desmopressin with resolution of hypernatremia. During the next five weeks of his 3-month hospitalization, he continued to have polyuria with specific gravity as low as 1.003 [1.005-1.030], and occasional hypernatremia, with a peak serum sodium of 150 mEq/L. Intranasal desmopressin as well as free water supplementation were given daily to alleviate his polyuria and hypernatremia. Evaluation of anterior pituitary function was normal except for decreased gonadotrophins. His polyuria resolved after five weeks, and labs showed urine osmolality of 530 mOsm/kg with serum sodium 138 mEq/L and urine specific gravity 1.010, consistent with resolution of CDI. Intranasal desmopressin was discontinued. His serum sodium remained stable without desmopressin for the next 7 weeks with serum sodium at discharge of 141 mEq/L. Discussion: The damage of the hypothalamic vasopressin-producing neurons, their axons or the posterior pituitary results in permanent post-TBI CDI. In cases of transient CDI, the pathogenesis is likely related to small vessel damage or inflammatory edema rather than direct neuronal damage. In our case, the patient initially developed hypernatremia and polyuria from acute CDI due to hemicraniectomy with debridement and washout. He continued to have prolonged transient CDI due to the extensive intracranial hemorrhage and edema. The CDI resolved with desmopressin (both intravenous and intranasal) and fluid replacement. Transient CDI is a rare complication intracranial haemorrhage. Our case highlights that the severity of TBI may correlate with the duration of transient CDI. Presentation: Friday, June 16, 2023

Basal skull fractures are associated with mortality in pediatric severe traumatic brain injury.

Basal skull fractures (BSFs) are caused by blunt force trauma, occurring in the temporal, occipital, sphenoid, and/or ethmoid bones. In pediatric severe traumatic brain injury (sTBI), there is a paucity of data on BSFs. Our goal was to investigate the BSF prevalence, anatomy, and association with short-term outcomes in pediatric sTBI. We retrospectively reviewed all severely injured (Injury Severity Score ≥12) pediatric patients (aged <18 years) admitted to our hospital after experiencing an sTBI (Glasgow Coma Scale score ≤8 and head Abbreviated Injury Scale score ≥4). Neuroimaging for all sTBI patients was reviewed for skull fractures. Data were analyzed with both univariate and multivariate techniques. Of the 180 patients with sTBI, 47 had BSFs for a prevalence of 26% (69 BSFs in total; 16 sTBI patients had ≥2 BSFs). The squamous temporal bone was fractured most frequently (n=30/47 sTBI patients with BSFs). Patients with BSFs were heavier and had more facial injuries than those without (p < 0.05) but were similar in all other admission demographics, injury profiles, and clinical characteristics. Cerebrospinal fluid leak was found in 32% (n = 15 of 47) of BSF patients (otorrhea, n = 12; rhinorrhea, n = 1; otorrhea/rhinorrhea, n = 2; p < 0.001). Mortality, acute central diabetes insipidus, and fewer ventilator-free days were associated with BSFs (p < 0.005), whereas in sTBI survivors, BSFs were associated with longer lengths of stay (p < 0.05). Multiple logistic regression showed that BSFs were positively associated with the presence of subarachnoid hemorrhage (odds ratio [OR], 4.00; p = 0.001), contusion (OR, 2.48; p = 0.029), herniation (OR, 3.40; p = 0.037), and cerebral edema (OR, 2.30; p = 0.047) but negatively associated with diffuse axonal injury (OR, 0.20; p = 0.003). BSFs and mortality were strongly associated (OR, 6.87; p = 0.019). BSFs occurred in 26% of pediatric sTBI patients. The temporal bone was fractured in two thirds of sTBI patients with BSFs, and one third was associated with cerebrospinal fluid leaks. BSFs represent a significant linear blunt force and are independent predictors of mortality. Prognostic and epidemiologic study, level III.

The role of serious concomitant injuries in the treatment and outcome of pediatric severe traumatic brain injury

The study objective was to describe the epidemiology of serious concomitant injuries and their effects on outcome in pediatric severe traumatic brain injury (sTBI). A retrospective cohort of all severely injured (Injury Severity Score [ISS] ≥ 12) pediatric patients (<18 years) admitted to our pediatric intensive care unit, between 2000 and 2011, after experiencing an sTBI (Glasgow Coma Scale [GCS] score ≤ 8 and head Abbreviated Injury Scale [AIS] ≥ 4) were included. Two groups were compared based on the presence of serious concomitant injuries (maximum AIS score ≥ 3). Multivariate logistic regression was undertaken to determine variable associations with mortality. Of the 180 patients with sTBI, 113 (63%) sustained serious concomitant injuries. Chest was the most commonly injured extracranial body region (84%), with lung being the most often injured. Patients with serious concomitant injuries had increased age, weight, and injury severity (p < 0.001) and were more likely injured in a motor vehicle collision (91% vs. 48%, p < 0.001). Those with serious concomitant injuries had worse sTBI, based on lower presedation GCS (p = 0.031), higher frequency of fixed pupils (p = 0.006), and increased imaging abnormalities (SAH and DAI, p ≤ 0.01). Non-neurosurgical operations and blood transfusions were more frequent in the serious concomitant injury group (p < 0.01). The differences in mortality for the two groups failed to reach statistical significant (p = 0.053), but patients with serious concomitant injuries had higher rates of infection and acute central diabetes insipidus, fewer ventilator-free days, and greater length of stays (p < 0.05). Multivariate analyses revealed fixed pupillary response (odd ratio [OR], 63.58; p < 0.001), presedation motor GCS (OR, 0.23; p = 0.001), blood transfusion (OR, 5.80; p = 0.008), and hypotension (OR, 4.82; p = 0.025) were associated with mortality, but serious concomitant injuries was not (p = 0.283). Head injury is the most important prognostic factor in mortality for sTBI pediatric patients, but the presence of serious concomitant injuries does contribute to greater morbidity, including longer stays, more infections, fewer ventilator-free days, and a higher level of care required on discharge from hospital. Prognostic and epidemiologic study, level III.

Central Diabetes Insipidus in Pediatric Severe Traumatic Brain Injury

To determine the occurrence rate of central diabetes insipidus in pediatric patients with severe traumatic brain injury and to describe the clinical, injury, biochemical, imaging, and intervention variables associated with mortality. Retrospective chart and imaging review. Children's Hospital, level 1 trauma center. Severely injured (Injury Severity Score ≥ 12) pediatric trauma patients (>1 month and <18 yr) with severe traumatic brain injury (presedation Glasgow Coma Scale ≤ 8 and head Maximum Abbreviated Injury Scale ≥ 4) that developed acute central diabetes insipidus between January 2000 and December 2011. Of 818 severely injured trauma patients, 180 had severe traumatic brain injury with an overall mortality rate of 27.2%. Thirty-two of the severe traumatic brain injury patients developed acute central diabetes insipidus that responded to desamino-8-D-arginine vasopressin and/or vasopressin infusion, providing an occurrence rate of 18%. At the time of central diabetes insipidus diagnosis, median urine output and serum sodium were 6.8 ml/kg/hr (interquartile range = 5-11) and 154 mmol/L (interquartile range = 149-159), respectively. The mortality rate of central diabetes insipidus patients was 87.5%, with 71.4% declared brain dead after central diabetes insipidus diagnosis. Early central diabetes insipidus onset, within the first 2 days of severe traumatic brain injury, was strongly associated with mortality (p < 0.001), as were a lower presedation Glasgow Coma Scale (p = 0.03), a lower motor Glasgow Coma Scale (p = 0.01), an occurrence of fixed pupils (p = 0.04), and a prolonged partial thromboplastin time (p = 0.04). Cerebral edema on the initial computed tomography, obtained in the first 24 hrs after injury, was the only imaging finding associated with death (p = 0.002). Survivors of central diabetes insipidus were more likely to have intracranial pressure monitoring (p = 0.03), have thiopental administered to induce coma (p = 0.04) and have received a decompressive craniectomy for elevated intracranial pressure (p = 0.04). The incidence of central diabetes insipidus in pediatric patients with severe traumatic brain injury is 18%. Mortality was associated with early central diabetes insipidus onset and cerebral edema on head computed tomography. Central diabetes insipidus nonsurvivors were less likely to have received intracranial pressure monitoring, thiopental coma and decompressive craniectomy.