The article by Cohen and Wolstenholme provides a useful overview of Penthrox but is unfortunately incomplete.
Compared with modern anaesthetic agents, Penthrox is an unclean drug and would not get a product license if invented today. The high fat solubility means a tissue reservoir persists for ≈1 week. About 70% is biotransformed, and this continues after administration until the tissue reservoir is empty. Nephrotoxicity was not just “a concern” but actually happened; ≈20 people died [1].
It has only been possible to use Penthrox 5 million times safely because of essential pre-use checks to ensure no contraindications. It is worth remembering that methoxyflurane was used 10-12 million times before the nephrotoxic potential was established [1].
Penthrox produces nephrotoxic metabolites at all doses, but this only becomes clinically significant above a certain level. The claim that Penthrox use is not nephrotoxic is technically correct, however, the presence of other factors that can also induce renal injury will reduce the Penthrox safety net. Of relevance to military use, this includes crush injury, hypovolaemic shock and patients subsequently requiring nephrotoxic antibiotics. Other potential issues for military use: (1) Limit to ≈50min administration (two bottles); (2) Activated charcoal adsorber is only effective IF the patient exhales through it. The patient will continue to exhale small amounts of drug for hours after administration; (3) There i...
The article by Cohen and Wolstenholme provides a useful overview of Penthrox but is unfortunately incomplete.
Compared with modern anaesthetic agents, Penthrox is an unclean drug and would not get a product license if invented today. The high fat solubility means a tissue reservoir persists for ≈1 week. About 70% is biotransformed, and this continues after administration until the tissue reservoir is empty. Nephrotoxicity was not just “a concern” but actually happened; ≈20 people died [1].
It has only been possible to use Penthrox 5 million times safely because of essential pre-use checks to ensure no contraindications. It is worth remembering that methoxyflurane was used 10-12 million times before the nephrotoxic potential was established [1].
Penthrox produces nephrotoxic metabolites at all doses, but this only becomes clinically significant above a certain level. The claim that Penthrox use is not nephrotoxic is technically correct, however, the presence of other factors that can also induce renal injury will reduce the Penthrox safety net. Of relevance to military use, this includes crush injury, hypovolaemic shock and patients subsequently requiring nephrotoxic antibiotics. Other potential issues for military use: (1) Limit to ≈50min administration (two bottles); (2) Activated charcoal adsorber is only effective IF the patient exhales through it. The patient will continue to exhale small amounts of drug for hours after administration; (3) There is no evidence that it is superior to other analgesics in current use. Its time profile differs from e.g. fentanyl lozenges, but not necessarily the quality of analgesia; (4) Any hangover from opioid can be easily reversed with naloxone. This is not possible with Penthrox; (5) Cardiovascular stability is not guaranteed, as suggested in the review, so the manufacturers have specifically made cardiovascular instability a contraindication.
Penthrox is metabolised to fluoride (and dichloroacetic acid, which may have a role in nephrotoxicity). Sevoflurane is metabolised to subtoxic levels of fluoride ion [1]. This may be enhanced by concurrent administration of enzyme-inducing drugs, as it is for Penthrox [2], including smoking [3], and related to duration of administration [3]. Sub-toxic fluoride levels of the two drugs could be additive, and it is this concern that led authorities to state that sevoflurane is contraindicated after Penthrox. The research to confirm or refute this has not yet been done.
The manufacturer has identified nine items to be checked before administering Penthrox. Other analgesics must therefore still be available for people who should not receive it. Conclusion: Penthrox can be another analgesic in the armamentarium, but it is not the answer on its own.
References
1. Mazze RI. Methoxyflurane revisited. Tale of an anesthetic from cradle to grave. Anesthesiology 2006; 105: 843-6
2. European Medicines Consortium. Penthrox 3mL inhalation vapour, liquid. Summary of Product Characteristics (Updated 14-Jan-2019. Galen Limited)
3. Cabibel C, Gerard L, Maiter D, Collin V, Hantson P. Complete nephrogenic diabetes insipidus after prolonged sevoflurane sedation: a case report of 3 cases. Anesth Analg Case Rep 2019; 12: 155-9
We read with interest the article by Bayoumy et al. concerning the effects of hyperbaric oxygen therapy (HBOT) associated with corticosteroid therapy in military personnel with acute acoustic trauma1. This paper helps to discuss about the most appropriate treatment of sudden deafness (SD). As recently stated, a spontaneous recovery, in the general population, is less than 40%. The precise role of HBOT has not yet been clearly established2. Our clinical experience during the last 15 years in a second referral hyperbaric center indicates the need of clear guide-lines, for the treatment of this acute disease. Nowadays there are two main therapeutic approaches to SD of different origin, the corticosteroid medication and HBOT.
Clearly, at first, it has to be ascertained the nature of a deafness excluding, cerebral diseases, vascular, traumatic and neoplastic. A subsequent otolaryngology evaluation enables to ascertain possible associated vestibular diseases, and to measure Pure Tone Average. Medical contraindications to HBOT and corticosteroids medication have to be excluded. An early treatment, not beyond the first 48 hours after the acute event is recommended 1. Today the HBOT standardized protocol, consists in a daily oxygen 100% at 2.2-2.5 atmosphere for 90 minutes, for a minimum of 10 sessions in case of satisfying functional recovery. On the contrary, in case of absolutely negative results, the treatment should be interrupted. Otherwise, HBOT can be prolonged to a...
We read with interest the article by Bayoumy et al. concerning the effects of hyperbaric oxygen therapy (HBOT) associated with corticosteroid therapy in military personnel with acute acoustic trauma1. This paper helps to discuss about the most appropriate treatment of sudden deafness (SD). As recently stated, a spontaneous recovery, in the general population, is less than 40%. The precise role of HBOT has not yet been clearly established2. Our clinical experience during the last 15 years in a second referral hyperbaric center indicates the need of clear guide-lines, for the treatment of this acute disease. Nowadays there are two main therapeutic approaches to SD of different origin, the corticosteroid medication and HBOT.
Clearly, at first, it has to be ascertained the nature of a deafness excluding, cerebral diseases, vascular, traumatic and neoplastic. A subsequent otolaryngology evaluation enables to ascertain possible associated vestibular diseases, and to measure Pure Tone Average. Medical contraindications to HBOT and corticosteroids medication have to be excluded. An early treatment, not beyond the first 48 hours after the acute event is recommended 1. Today the HBOT standardized protocol, consists in a daily oxygen 100% at 2.2-2.5 atmosphere for 90 minutes, for a minimum of 10 sessions in case of satisfying functional recovery. On the contrary, in case of absolutely negative results, the treatment should be interrupted. Otherwise, HBOT can be prolonged to a maximum of 30 sessions, mainly in case of persisting vestibular signs or slow but progressive recovery. We underline the importance of an early corticosteroid treatment at the onset of clinical signs; it should be prolonged in the first ten HBOT sessions.
All this correlates to patho-physiological bases. The inner ear has limited possibility of collateral vascular network evident in case of acute ischemia/sub-ischemia, always considering that a constant 02 supply can prevent neuronal damage. HBOT increases the rate of diffused 02, opposes to the activation of inflammatory cascades, decreasing the release of pro-inflammatory cytokines, in particular alfa -TNF, IL 1, 1b and 6. At the same time, it improves the tissue concentration of anti-inflammatory IL-10 and heat shock protein 90, so reducing a precocious apoptosis3. Furthermore, the contemporary corticosteroid treatment helps to reduce the entire inflammatory process favoring a better functional recovery. Therefore HBOT cannot be considered a second line treatment, applied after failure of other therapeutic measures, but as first line even better associated with corticosteroids.
References
1) Bayoumy AB, van der Veen EL, van Ooij P-JAM, et al. J R Army Med Corps 2019; doi:10.1136/jramc-2018-001117
2) De Ru JA Bayoumy AB. Sudden deafness: hyperbaric oxygen therapy should be discussed. BMJ 2019;364;1758.
3)Muzzi, E., Zennaro, B., Visentin, et al. Hyperbaric oxygen therapy as salvage treatment for sudden sensorineural hearing loss: Review of rationale and preliminary report. J Laryngol Otol 2010;124(2) E2.
Critical Care Air Transport Team and traumatic brain injury
Viroj Wiwanitkit1
1. Hainan Medical University, China
Correspondence
Professor Viroj Wiwanitkit
Email: wviroj@yahoo.com
I read this article on the "Critical Care Air Transport Team and traumatic brain injury" with a great interest [1]. Boyd et al. noted that "Air transport personnel must be prepared to provide standard critical care but also care specific to TBIs, including ICP control and management of diabetes insipidus. Although these patients and their potential complications are traditionally managed by neurosurgeons, those providers without neurosurgical backgrounds can be provided this training to help fill a wartime need." I agree that in the critical situation and resource limited (such as remote area or war zone), the use of available facilities and personnel is better than doing nothing or waiting for the specialty. For the military clinical practice, the question is on the skill of the medical military personnel. There should a specific training for any medical military personnel on this specific subject, which is different from non-military ones. Another interesting question that I and many readers might want to know is on the safety management of the medical personnel and military team in the war zone. The summary of experience on self-protection during caring the others will be a useful data. Referring...
Critical Care Air Transport Team and traumatic brain injury
Viroj Wiwanitkit1
1. Hainan Medical University, China
Correspondence
Professor Viroj Wiwanitkit
Email: wviroj@yahoo.com
I read this article on the "Critical Care Air Transport Team and traumatic brain injury" with a great interest [1]. Boyd et al. noted that "Air transport personnel must be prepared to provide standard critical care but also care specific to TBIs, including ICP control and management of diabetes insipidus. Although these patients and their potential complications are traditionally managed by neurosurgeons, those providers without neurosurgical backgrounds can be provided this training to help fill a wartime need." I agree that in the critical situation and resource limited (such as remote area or war zone), the use of available facilities and personnel is better than doing nothing or waiting for the specialty. For the military clinical practice, the question is on the skill of the medical military personnel. There should a specific training for any medical military personnel on this specific subject, which is different from non-military ones. Another interesting question that I and many readers might want to know is on the safety management of the medical personnel and military team in the war zone. The summary of experience on self-protection during caring the others will be a useful data. Referring to the terrorism in many areas around the world, the medical personnel are often focused as a target for attacking.
Conflict of interest
None
References
1. Boyd LR, Borawski J, Lairet J, Limkakeng AT Jr. Critical Care Air Transport Team severe traumatic brain injury short-term outcomes during flight for Operation Iraqi Freedom/Operation Enduring Freedom. J R Army Med Corps. 2017 Apr 6. pii: jramc-2016-000743. doi: 10.1136/jramc-2016-000743. [Epub ahead of print]
The article by Cohen and Wolstenholme provides a useful overview of Penthrox but is unfortunately incomplete.
Compared with modern anaesthetic agents, Penthrox is an unclean drug and would not get a product license if invented today. The high fat solubility means a tissue reservoir persists for ≈1 week. About 70% is biotransformed, and this continues after administration until the tissue reservoir is empty. Nephrotoxicity was not just “a concern” but actually happened; ≈20 people died [1].
It has only been possible to use Penthrox 5 million times safely because of essential pre-use checks to ensure no contraindications. It is worth remembering that methoxyflurane was used 10-12 million times before the nephrotoxic potential was established [1].
Penthrox produces nephrotoxic metabolites at all doses, but this only becomes clinically significant above a certain level. The claim that Penthrox use is not nephrotoxic is technically correct, however, the presence of other factors that can also induce renal injury will reduce the Penthrox safety net. Of relevance to military use, this includes crush injury, hypovolaemic shock and patients subsequently requiring nephrotoxic antibiotics. Other potential issues for military use: (1) Limit to ≈50min administration (two bottles); (2) Activated charcoal adsorber is only effective IF the patient exhales through it. The patient will continue to exhale small amounts of drug for hours after administration; (3) There i...
Show MoreWe read with interest the article by Bayoumy et al. concerning the effects of hyperbaric oxygen therapy (HBOT) associated with corticosteroid therapy in military personnel with acute acoustic trauma1. This paper helps to discuss about the most appropriate treatment of sudden deafness (SD). As recently stated, a spontaneous recovery, in the general population, is less than 40%. The precise role of HBOT has not yet been clearly established2. Our clinical experience during the last 15 years in a second referral hyperbaric center indicates the need of clear guide-lines, for the treatment of this acute disease. Nowadays there are two main therapeutic approaches to SD of different origin, the corticosteroid medication and HBOT.
Show MoreClearly, at first, it has to be ascertained the nature of a deafness excluding, cerebral diseases, vascular, traumatic and neoplastic. A subsequent otolaryngology evaluation enables to ascertain possible associated vestibular diseases, and to measure Pure Tone Average. Medical contraindications to HBOT and corticosteroids medication have to be excluded. An early treatment, not beyond the first 48 hours after the acute event is recommended 1. Today the HBOT standardized protocol, consists in a daily oxygen 100% at 2.2-2.5 atmosphere for 90 minutes, for a minimum of 10 sessions in case of satisfying functional recovery. On the contrary, in case of absolutely negative results, the treatment should be interrupted. Otherwise, HBOT can be prolonged to a...
Critical Care Air Transport Team and traumatic brain injury
Viroj Wiwanitkit1
1. Hainan Medical University, China
Correspondence
Professor Viroj Wiwanitkit
Email: wviroj@yahoo.com
I read this article on the "Critical Care Air Transport Team and traumatic brain injury" with a great interest [1]. Boyd et al. noted that "Air transport personnel must be prepared to provide standard critical care but also care specific to TBIs, including ICP control and management of diabetes insipidus. Although these patients and their potential complications are traditionally managed by neurosurgeons, those providers without neurosurgical backgrounds can be provided this training to help fill a wartime need." I agree that in the critical situation and resource limited (such as remote area or war zone), the use of available facilities and personnel is better than doing nothing or waiting for the specialty. For the military clinical practice, the question is on the skill of the medical military personnel. There should a specific training for any medical military personnel on this specific subject, which is different from non-military ones. Another interesting question that I and many readers might want to know is on the safety management of the medical personnel and military team in the war zone. The summary of experience on self-protection during caring the others will be a useful data. Referring...
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