Clozapine is the drug of choice for patients with an unsatisfactory response to classic antipsychotic treatment. Little is known about the involvement of clozapine in the development of parotid disease.

Identify the clinical characteristics of Clozapine-induced parotitis through a case and literature review.

We report the case of a patient with a refractory schizoaffective disorder, bipolar type and who developed recurrent parotitis while taking clozapine. We conducted a literature review based on a PubMed search of articles published on this subject with the following keywords: ‘parotitis clozapine’.

Miss W., 34 years old, suffers from a severe schizoaffective disorder that has been diagnosed for several years. She has received various psychotropic medications. She suffered from frequent relapses that required recurrent hospital admissions. One year ago, a diagnosis of treatment-resistant schizoaffective disorder was made. The decision to introduce clozapine, associated with mood stabilizer treatment, was made on the basis of her treatment refractory symptoms. She experienced considerable sialorrhea after beginning clozapine treatment. Miss W. developed bilateral recurrent swelling over both temporal-mandibular areas after 6 months of treatment. It often appears after eating and lasts from 4 to 6 hours. There was no change in white blood cell count and she was afebrile. An otolaryngologist was consulted and a diagnosis of clozapine-induced parotitis was suggested. A spasmolytic and an anticholinergic treatment were prescribed and clozapine was continued.

This iatrogenic effect of clozapine must be recognized by clinicians in order to be better prevented.

Recent studies have brought to question the efficacy of the use of prehospital therapeutic hypothermia for victims of out-of-hospital cardiac arrest (OHCA). Though guidelines recommend therapeutic hypothermia as a critical link in the chain of survival, the safety of this intervention, with the possibility of minimal treatment benefit, becomes important.

This study examined prehospital therapeutic hypothermia for OHCA, its association with survival, and its complication profile in a large, metropolitan, fire-based Emergency Medical Services (EMS) system, where bystander cardiopulmonary resuscitation (CPR) and post-arrest care are in the process of being optimized.

This evaluation was a retrospective chart review of all OHCA patients with return of spontaneous circulation (ROSC) treated with therapeutic hypothermia, from January 1, 2013 through November 30, 2013. The primary outcomes were the proportion of patients with initiation of prehospital therapeutic hypothermia with survival to hospital admission, the proportion of patients with initiation of prehospital therapeutic hypothermia with survival to hospital discharge, and the complication profile of therapeutic hypothermia in this population. The complication profile included several clinical, radiographic, and laboratory parameters. Exclusion criteria included: no prehospital therapeutic hypothermia initiation; no ROSC; and age of 17 year old or younger.

Fifty-one post-cardiac arrest patients were identified that met inclusion criteria. The mean age was 61 years (SD=14.7 years), and 33 (72%) were male. The initial rhythm was ventricular fibrillation or pulseless ventricular tachycardia in 17 (37%) patients, and bystander CPR was performed in 28 (61%) patients with ROSC. Thirty-nine (85%) patients survived to hospital admission. Twenty-one patients (48%; 95% CI, 33-64) were administered vasopressors, 10 patients (24%; 95% CI, 10-37) were administered diuretics, and 19 patients (44%; 95% CI, 29-60) were administered antibiotics. Initial chest radiograph (CXR) findings were normal in 12 (29%) patients. Overall, 13 (28%; 95% CI, 15-42) study patients survived to hospital discharge.

Recent reports have questioned the efficacy and safety of prehospital therapeutic hypothermia. In this evaluation, in the setting of unstandardized post-arrest care, 85% of the patients survived to hospital admission and 28% survived to hospital discharge, with a complication profile which was similar to that noted in other studies. This suggests that further evidence may be needed before EMS systems stop administering therapeutic hypothermia to appropriately selected patients. In less-optimized systems, therapeutic hypothermia may still be an essential link in the chain of survival.

CortezE , PanchalAR , DavisJ , ZeebP , KesegDP . Clinical Outcomes in Cardiac Arrest Patients Following Prehospital Treatment with Therapeutic Hypothermia. Prehosp Disaster Med2015; 30(5):452–456.

Prehospital postresuscitation induced hypothermia (IH) has been shown to reduce neurological complications in comatose cardiac-arrest survivors. Retrofitting ambulances to include equipment appropriate to initiate hypothermia, such as refrigeration units for cooled saline, is expensive. The objective of this nonhuman subject research study was to determine if inexpensive, commercially available coolers could, in conjunction with five reusable ice packs, keep two 1 L bags of precooled 0.9% normal saline solution (NSS) at or below 4°C for an average shift of eight to 12 hours in a real-world environment, on board in-service Emergency Medical Service (EMS) units, over varying weather conditions in all seasons.

The coolers were chosen based on availability and affordability from two nationally available brands: The Igloo MaxxCold (Igloo Products Corp., Katy, Texas USA) and Coleman (The Coleman Company, Wichita, Kansas USA). Both are 8.5 liter (nine-quart) coolers that were chosen because they adequately held two 1 L bags of saline solution, along with the reusable ice packs designated in the study design, and were small enough for ease of placement on ambulances. Initial testing of the coolers was conducted in a controlled environment. Thereafter, each EMS unit was responsible to cool the saline to less than 4°C prior to shift. Data were collected by emergency medical technicians, paramedics, and resident physicians working in seven different ambulance squads. Data analysis was performed using repeated measurements recorded over a 12-hour period from 19 individual coolers and were summarized by individual time points using descriptive statistics.

Initial testing determined that the coolers maintained temperatures of 4°C for 12 hours in a controlled environment. On the ambulances, results based on the repeated measurements over time revealed that the saline solution samples as defined in the protocol, remained consistently below 4°C for 12 hours. Utilizing the lower bound of the 2-sided 95% exact binomial confidence intervals, there was less than a five percent chance that saline samples could not be maintained below 4°C for 12 hours, even during the summer months.

Simple, commercially available coolers can maintain two 1 L bags of 0.9% NSS at 4°C for 12 hours in ambulances in varying environmental conditions. This suggests that EMS agencies could inexpensively initiate prehospital IH in appropriate cases.

KaneKE , TomshoRJ , PheasantK , StaufferT , SchoenfeldtB , HamiltonS , KainT , KaneBG . The “ICE” Study: Feasibility of Inexpensive Commercial Coolers on Mobile EMS Units. Prehosp Disaster Med. 2014;29(3):1-8.

During the past 7 years, considerable new evidence has accumulated supporting the use of prophylactic hypothermia for traumatic brain injury (TBI). Studies can be divided into 2 broad categories: studies with protocols for cooling for a short, predetermined period (e.g., 24–48 h), and those that cool for longer periods and/or terminate based on the normalization of intracranial pressure (ICP). There have been no systematic reviews of hypothermia for TBI that include this recent new evidence.

This analysis followed the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and the QUOROM (quality of reporting of meta-analyses) statement. We developed a comprehensive search strategy to identify all randomized controlled trials (RCTs) comparing therapeutic hypothermia with standard management in TBI patients. We searched Embase, MEDLINE, Web of Science, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, ProceedingsFirst and PapersFirst. Additional relevant articles were identified by hand-searching conference proceedings and bibliographies. All stages of study identification and selection, quality assessment and analysis were conducted according to prospectively defined criteria. Study quality was determined by assessment of each study for the use of allocation concealment and outcome assessment blinding. Studies were divided into 2 a priori–defined subgroups for analysis based on cooling strategy: short term (≤ 48 h), and long term or goal-directed (> 48 h and/or continued until normalization of ICP). Outcomes included mortality and good neurologic outcome (defined as Glasgow Outcome Scale score of 4 or 5). Pooling of primary outcomes was completed using relative risk (RR) and reported with 95% confidence intervals (CIs).

Of 1709 articles, 12 studies with 1327 participants were selected for quantitative analysis. Eight of these studies cooled according to a long-term or goal-directed strategy, and 4 used a short-term strategy. Summary results demonstrated lower mortality (RR 0.73, 95% CI 0.62–0.85) and more common good neurologic outcome (RR 1.52, 95% CI 1.28–1.80). When only short-term cooling studies were analyzed, neither mortality (RR 0.98, 95% CI 0.75–1.30) nor neurologic outcome (RR 1.31, 95% CI 0.94–1.83) were improved. In 8 studies of long-term or goal-directed cooling, mortality was reduced (RR 0.62, 95% CI 0.51–0.76) and good neurologic outcome was more common (RR 1.68, 95% CI 1.44–1.96).

The best available evidence to date supports the use of early prophylactic mild-to-moderate hypothermia in patients with severe TBI (Glasgow Coma Scale score ≤ 8) to decrease mortality and improve rates of good neurologic recovery. This treatment should be commenced as soon as possible after injury (e.g., in the emergency department after computed tomography) regardless of initial ICP, or before ICP is measured. Most studies report using a temperature of 32°–34°C. The maximal benefit occurred with a long-term or goal-directed cooling protocol, in which cooling was continued for at least 72 hours and/or until stable normalization of intracranial pressure for at least 24 hours was achieved. There is large potential for further research on this therapy in prehospital and emergency department settings.