Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs: A multi‐center randomized parallel group clinical study

Charalambous, Marios; Volk, Holger A.; Tipold, Andrea; Erath, Johannes; Huenerfauth, Enrice I.; Gallucci, A.; Gandini, Gualtiero; Hasegawa, Daisuke; Pancotto, Theresa E.; Rossmeisl, John H.; Platt, Simon; Risio, Luisa De; Coates, Joan R.; Musteață, Mihai; Tirrito, Federica; Cozzi, Francesca; Porcarelli, Laura; Corlazzoli, Daniele; Cappello, Rodolfo; Vanhaesebrouck, An; Broeckx, Bart J. G.; Ham, Luc Van; Bhatti, Sofie

doi:10.1111/jvim.15627

Cited by 20 publications

(51 citation statements)

References 86 publications

(117 reference statements)

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“…This fast to immediate action has been supported by other studies ( 49 – 51 ) and is one of the reasons why the 5-min time frame was used for KET IV injection to be considered successful at terminating ictal activity and separate from other IV injections in this retrospective study. Five minutes has been used as the time limit to consider treatment successful in previous veterinary studies on canine SE ( 21 , 52 ). Most drugs injected IV within the context of SE, including DZ, are expected to be successful within that period ( 9 , 53 , 54 ), and it is also a frequent time frame for emergency clinicians to reach for another therapeutic option if the last one was unsuccessful.…”

Section: Discussionmentioning

confidence: 99%

Intravenous Ketamine Bolus(es) for the Treatment of Status Epilepticus, Refractory Status Epilepticus, and Cluster Seizures: A Retrospective Study of 15 Dogs

Roynard

Bilderback

Dewey³

2021

Front. Vet. Sci.

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Status epilepticus (SE) and cluster seizures (CS) are common occurrences in veterinary neurology and frequent reasons of admission to veterinary hospitals. With prolonged seizure activity, gamma amino-butyric acid (GABA) receptors (GABAa receptors) become inactive, leading to a state of pharmacoresistance to benzodiazepines and other GABAergic medications, which is called refractory status epilepticus (RSE). Prolonged seizure activity is also associated with overexpression of N-methyl-D-aspartic (NMDA) receptors. Rodent models have shown the efficacy of ketamine (KET) in treating RSE, and its use has been reported in one canine case of RSE. Boluses of KET 5 mg/kg IV have become the preferred treatment for RSE in our hospital. A retrospective study was performed to evaluate and report our experience with KET IV bolus to treat prolonged and/or repeated seizure activity in cases of canine CS, SE, and RSE. A total of 15 dogs were retrieved, for 20 hospitalizations and 28 KET IV injections over 3 years. KET IV boluses were used 12 times for RSE (9 generalized seizures, 3 focal seizures) and KET terminated the episode of RSE 12/12 times (100%); however, seizures recurred 4/12 times (33%) within ≤6 h of KET IV bolus. When used for CS apart from episodes of RSE, KET IV bolus was associated with termination of the CS episode only 4/14 times (29%). Only 4/28 (14%) KET IV boluses were associated with adverse effects imputable only to the use of KET. One dog experienced a short, self-limited seizure activity during administration of KET IV, which was most likely related to a pre-mature use of KET IV (i.e., before GABAergic resistance and NMDA receptor overexpression had taken place). This study indicates that KET 5 mg/kg IV bolus may be successful for the treatment of RSE in dogs.

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Section: Discussionmentioning

confidence: 99%

Intravenous Ketamine Bolus(es) for the Treatment of Status Epilepticus, Refractory Status Epilepticus, and Cluster Seizures: A Retrospective Study of 15 Dogs

Roynard

Bilderback

Dewey³

2021

Front. Vet. Sci.

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“…Midazolam's unique solubility characteristics (water soluble injection but with high lipophilicity at body pH) give it a very rapid onset of action after injection (Plumb, 2008). Although midazolam IV provides the quickest onset of action (Plumb, 2008), IN route provides superiority when the time needed to place an IV catheter is taken into account and same efficacy (Charalambous et al, 2019). Midazolam IM is rapidly and completely absorbed, in contrast with diazepam IM.…”

Section: Appraisal Application and Reflectionmentioning

confidence: 99%

In dogs with metaldehyde intoxication, are benzodiazepines more effective than methocarbamol in relaxing muscles and reducing tremors?

Liatis

2020

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PICO question In dogs with metaldehyde intoxication, are benzodiazepines (e.g. diazepam, midazolam) more effective than methocarbamol in relaxing muscles and reducing tremors? Clinical bottom line Category of research question Treatment The number and type of study designs reviewed Five papers were critically reviewed. There were five retrospective case series Strength of evidence Weak Outcomes reported Currently, five retrospective case series exist in the literature which discuss metaldehyde intoxication cases treated mainly with benzodiazepines, a few of which had methocarbamol. There is not really any study to compare directly benzodiazepines with methocarbamol. In addition to that, factors such as commercial (e.g. the low availability of methocarbamol in the UK market compared to the US market), administrational (e.g. multiple administration routes of benzodiazepines) and pharmacological (e.g. lack of anticonvulsant function of methocarbamol), have played an important role in the treatment choice. Several case reports exist as well Conclusion Currently, there is insufficient evidence to determine whether benzodiazepines are more effective than methocarbamol in relaxing muscles and reducing occurrence of muscle tremors How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision-making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

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“…In veterinary medicine, MDZ and DZP have been mainly used, although only DZP is currently licenced for small animals. In dogs, both DZP and MDZ can be effective for ceasing seizure activity, but this can depend on the administration route and dose [ 5 , 22 , 23 , 25 ]; the recommended dose ranges for MDZ or DZP remain the same regardless the route of administration. Although not well-defined, it has been estimated that DZP should reach serum concentration of 0.15–0.5 μg/mL [ 33 , 51 – 53 ] within 10–15 min in order to provide a clinically acceptable seizure control in canine SE and prevent progression to more refractory stages.…”

Section: Introductionmentioning

confidence: 99%

“…i.e. liver-induced drug metabolism whereby the concentration of a drug might be substantially reduced) [ 30 , 56 ], and is likely effective for ceasing SE in humans [ 63 – 71 ] and dogs [ 23 , 25 , 33 , 72 – 74 ]. In humans, IV administration of BDZs has been considered the “gold standard” route as it can result in the highest drug efficacy and shorter seizure cessation time [ 75 – 77 ]; similar recommendations have been made in dogs [ 25 , 78 ].…”

Section: Introductionmentioning

confidence: 99%

First-line management of canine status epilepticus at home and in hospital-opportunities and limitations of the various administration routes of benzodiazepines

et al. 2021

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Status epilepticus (SE) or prolonged epileptic seizure activity is a common neurological emergency with a high mortality rate and, if left untreated, can lead to irreversible cerebral damage and systemic complications. Fast and effective first-line management is of paramount importance, particularly in the at-home management of seizures where drug administration routes are limited. Benzodiazepines (BZDs) have been exclusively used in veterinary medicine for decades as first-line drugs based on their high potency and rapid onset of action. Various administration routes exist in dogs, such as oral, intravenous, intramuscular, rectal, and intranasal, all with different advantages and limitations. Recently, intranasal drug delivery has become more popular due to its unique and favourable characteristics, providing potential advantages over other routes of drug administration in the management of canine SE. This narrative review provides an outline of the management of SE at home and in a hospital setting, discusses considerations and challenges of the various routes of BZD administration, and evaluates the impact of intranasal drug administration (nose-brain pathway) for controlling canine SE at home and within hospital settings.

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Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs: A multi‐center randomized parallel group clinical study

Cited by 20 publications

References 86 publications

Intravenous Ketamine Bolus(es) for the Treatment of Status Epilepticus, Refractory Status Epilepticus, and Cluster Seizures: A Retrospective Study of 15 Dogs

Intravenous Ketamine Bolus(es) for the Treatment of Status Epilepticus, Refractory Status Epilepticus, and Cluster Seizures: A Retrospective Study of 15 Dogs

In dogs with metaldehyde intoxication, are benzodiazepines more effective than methocarbamol in relaxing muscles and reducing tremors?

First-line management of canine status epilepticus at home and in hospital-opportunities and limitations of the various administration routes of benzodiazepines

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