Hypercapnic encephalopathy causes mental confusion in humans. Diagnosis is with arterial blood gas tests. Depressed ventilation [the motor part of breathing] and mental confusion, strongly suggests the need for an ABG test in order to check for retention of C02. Co2 is a normal product of cell metabolism and the brain tracks it carefully, as it is a strong cerebral dilator and can increase intracranial pressure. [see research listed in earlier blogs] .
“C02 has a complex effect on the CNS: it powerfully and rapidly enhances CBF, increases the rate of CSF production, and may alter blood-brain barrier permeability. Functionally, C02 augments seizure threshold in rats, causes clouding in mentation processes and induces retrograde amnesia.…………………………….symptomatology is reversible, and it abates on return to normacapnia. Accordingly, hypercapnia does not elicit cerebral damage. Experimentally, even extreme hypercapnia [at a Pa C02 of 300 mm Hg] with associated with grave tissue acidosis, produces minor brain alteration [such as slight chromatin clumping and mitochondrial swelling] so that irreversible cell damage is unlikely. “ Handbook of Neurochemistry Pathological Neurochemistry 10 [ed] Abel Lajtha, Springer : Science and Business Media, 2013, Chapter 26, Page 715 , 716 Metabolic Encephalopathy; Encephalopathies from organ and system pathology; Respiratory Encephalopathies: Hypercapnia.
Metabolic Encephalopathies [ME ] are dreaded complications of very common diseases such as hepatic, renal or respiratory failure and are vey complicated and need a lot more research. It is very possible that in the near future we will understand most severe mental illness syndromes to be caused by one or more of the many metabolic encephalopathies. To be successful in this goal, one may want to start to look for disturbances in baseline resting respiratory rates in all patients who are have become functionally impaired by insanity, depression, delirium, dementia, altered mental status, madness, etc…all synonyms for patterns of memory loss and brain dysfunction and locomotor effects [inhibited locomotor activity, excited and/or uninhibited locomotor activity, mixed] affecting patients.
Changes to respiratory rates and abnormal respiratory rates [depressed or excited] are the most sensitive markers of abnormal physiology. ”
Respiratory rate: the neglected vital sign -Michelle A Cretikos, Rinaldo Bellomo, Ken Hillman, Jack Chen, Simon Finfer and Arthas Flabouris Med J Aust 2008; 188 (11): 657-659. || doi: 10.5694/j.1326-5377.2008.tb01825.x
- The level of documentation of vital signs in many hospitals is extremely poor, and respiratory rate, in particular, is often not recorded.
- There is substantial evidence that an abnormal respiratory rate is a predictor of potentially serious clinical events.
- Nurses and doctors need to be more aware of the importance of an abnormal respiratory rate as a marker of serious illness.
- Hospital systems that encourage appropriate responses to an elevated respiratory rate and other abnormal vital signs can be rapidly implemented. Such systems help to raise and sustain awareness of the importance of vital signs. Respiratory rate: the neglected vital sign -Michelle A Cretikos, Rinaldo Bellomo, Ken Hillman, Jack Chen, Simon Finfer and Arthas Flabouris Med J Aust 2008; 188 (11): 657-659. || doi: 10.5694/j.1326-5377.2008.tb01825.x
Rather than responding to to depressed, delirious and demented patients with dread and despair and fear, as doctors and psychiatrists inevitably do, when treatments are inadequate and they don’t know what to do, more work and more research and investigations of abnormal physiology and pathological neurochemistry is the only way forward. Once the pathogenic mechanisms of most ME’s [metabolic encephalopathies] are more clearly understood, than specific supportive medical treatments and even prevention [of ME’s] can be successful. And this may hold true for the seriously incapacitating incorrectly named “mental” illnesses, many of which will certainly turn out to be syndromes of metabolic encephalopathy upon closer medical investigations.[in Paula’s opinion].[mine too].
But first, doctors and scientist must get past their biases, and then they will have to overcome their fear and their hopelessness. And they need to spend one minute counting respiratory rate of their confused and cognitively impaired patients. If RR at rest is abnormal [too slow, too fast] , then they need to get tidal volume and minute ventilation and if necessary ABG tests.
Paula’s doctor did not feel fear and hopelessness at all, because he got it all wrong; because he neglected to work her up properly. He never found out that her respiratory rate was depressed or that she suddenly had an acute episode of retrograde amnesia …[she woke up one day and no longer remembered how to do her job, could not retain her thoughts long enough to tell him and she forgot how to conduct social conversations.with friends and family ]. … The doctor thought that she was depressed, instead of reversibly demented. That was encouraging for him, I guess, but not for Paula.
Paula and I still managed to help her by tracking which treatments helped recover her memory over time….it was a sloppy method and it took way too long [ten years to recover stable baseline mentation and memory] with way too many side effects at first but we succeeded where her doctors failed.
Thanks to Kraepelin’s prospective long term studies of similar patients [thousands of them], we knew that it was possible for Paula to recover her mental abilities and her memory completely……Chapter One, Manic Depressive Insanity Emile Kraepelin 1926. [see earlier blogposts for the complete reference. ” Basically Kraepelin’s description of this syndrome was that of a chronic delirium [all 3 locomotor subtypes]. It only rarely caused death in the otherwise strong young adults he examined.
Kraepelin’s physical examination of his bipolar depressed and manic patients suggested ventilatory failure due to depressed and otherwise abnormal respiration rates and psychomotor slowing or excitement. . Ventilatory failure can result in hypercapnia.
“ Usually, this [neurological] symptomatology [of hypercapnia] is reversible, and it abates on return to normacapnia. Accordingly, hypercapnia does not elicit cerebral damage.“Handbook of Neurochemistry Pathological Neurochemistry 10 [ed] Abel Lajtha, Springer : Science and Business Media, 2013, Chapter 26, Page 715 , 716 Metabolic Encephalopathy; Encephalopathies from organ and system pathology; Hypercapnia. Respiratory Encephalopathies:
Paula and I have suggested, based on her experience, that this insanity [distress and anguish/ euphoria, irritability ] and strange behavior is due to a retrospective memory loss and autobiographical amnesia, due to the ultimately reversible effects of hypercapnia, a metabolic encephalopathy due to failure of the ventilatory system.
“Metabolic Encephalopathies [ME’s] constitute a chapter of of increasing interest in human pathology since they are dreaded complications of very common diseases such as hepatic, renal, or respiratory failure. At times ME’s may represent the factor limiting the survival of patients in spite of advances in the treatment of the underlying disease. …………… This derives from the fact that, up to now, the pathogenic mechanisms of most ME’s have not been clearly delineated. Thus, the specific therapy and/or the prevention is far from satisfactory.
Obviously, not all ME’s will be discussed; space limitations impose a selection. The reader , therefore is referred to other chapters of this handbook for discussion of ME’s not included in this review. ……….
….…Encephalopathies from organ and system pathology; Respiratory Encephalopathies: Hypercapnia, directly or indirectly through acidosis, might play an important role in producing cerebral metabolic abnormalities and related neurological features, which, in turn, depend on the type of hypercapnia, i.e. acute, chronic or severe.
C02 has a complex effect on the CNS: it powerfully and rapidly enhances CBF, increases the rate of CSF production, and may alter blood-brain barrier permeability. Functionally, C02 augments seizure threshold in rats, causes clouding in mentation processes and induces retrograde amnesia.
Depending on the duration and severity, hypercapnia alters cerebral metabolites: for instance, moderate reductions of pyruvate, lactate, citrate, a-ketoglutarate, and malate have all been reported. It is likely that such alterations could be ascribed to the inhibition of pH dependent cerebral enzymes.
The impairment of cerebral metabolism is related to EEG changes seen during severe hypercapnia. Hypercapnia does not affect the cerebral metabolic rate for 02, whereas glucose utilization is depressed, owing to the inhibition of phosphofructokinase, probably mediated by C02-induced acidosis. However, other mechanisms should be invoked since glucose-6-phosphate returns to its normal level after 60 minutes of hypercapnia, when glucose utilization is still inhibited.
Since the brain energy balance, i.e. ATP and ADP concentrations, is unchanged, it appears that the brain utilizes other metabolites than glucose for its energy requirements. The reduced brain concentration of glutamic and aspartic acids, along with an enhanced production of ammonia and glutamine, may indicate that oxidation of those amino acids could represent a source of energy for the brain.
In some cases ammonia levels were also found to be increased in the plasma of patients with chronic or pulmonate and neurological symptoms, suggesting a role of ammonia in producing respiratory encephalopathy, although up to now no significant correlation has been clearly established. All the above alterations may contribute to the neurological derangement observed during respiratory failure. Individuals with chronic respiratory diseases may adapt to chronic hypercapnia, and its effects may be different from those produced by the acute form; for instance, in pneumatic patients, CBF does not increase in proportion to hypercapnia, where it does occur in patients without pneumopathies. In addition, during prolonged experimental hypercapnia, which more closely mimics hypercapnia induced by pulmonary insufficiency, alterations of brain oxygen consumption, CBF,pH, and blood-brain barrier do not occur. Chronic hypercapnia enhances glutamine and GABA cerebral content, decreases glutamate and aspartate, and induces moderne brain edema. These changes may modify brain excitability and may be causative of the neurological disturbances associated with chronic pulmonary failure.
Usually, this symptomatology is reversible, and it abates on return to normacapnia. Accordingly, hypercapnia does not elicit cerebral damage. Experimentally, eve extreme hypercapnia [at a Pa C02 of 300 mm Hg] with associated with grave tissue acidosis, produces minor brain alteration [such as slight chromatin clumping and mitochondrial swelling] so that irreversible cell damage is unlikely. ” Handbook of Neurochemistry Pathological Neurochemistry 10 [ed] Abel Lajtha, Springer : Science and Business Media, 2013, Chapter 26 Page 715 , 716 Metabolic Encephalopathy; Encephalopathies from organ and system pathology; Respiratory Encephalopathies: Hypercapnia.
Encephalopathy is a common and sometimes a presenting feature of decompensated chronic respiratory failure. There is a wide number of clinical and paraclinical signs of this condition and four grades of severity without a close correlation with blood gas changes. This condition is the consequence of complex metabolic and circulatory disturbances resulting from the blood gas abnormalities. The prognosis is good when the respiratory failure is quickly and correctly treated. Ann Med Interne (Paris). 1986;137(3):238-43. [Respiratory encephalopathy] N Delorme, P Sadoul PMID: 3767193
No one investigated Paula for a possible ME. No one obtained her vital signs. No one counted her baseline resting respiratory rate. No one knew her breathing was depressed. No one got her an Arterial Blood Gas Test. No one gave her a mental status test. No one understood how confused she was. No one understood that she had retrograde amnesia and that this was the reason why she was not her normal self. These things are not hard to do in the twenty first century.
Paula had no idea what was wrong with her and badly needed a doctor to help. No one asked for her birth history or medical history or her * early life occupational exposure history. All turned out to be very pertinent to her diagnosis. We were the only ones to find out all this about Paula.
- Recognizing Occupational Disease—Taking an Effective Occupational History Am Fam Physician. 1998 Sep 15;58(4):935-944. MICHAEL B. LAX, WILLIAM D. GRANT, . FEDERICA A. MANETTI, and ROSEMARY KLEIN
This is the kind of medical workup that should be required for all patients who look like they have major depression or bipolar depression/mania or a lingering delirium, dementia and/or significant cognitive impairment. Doctors learn all this in medical school. And they forget it when they practice with real patients with scary symptoms like mental confusion.
Paula did not receive this kind of medical workup. If a doctor would have done a proper job, instead of jumping to biased conclusions based on non specific mood and psychological behavior, the diagnosis and the treatment would have been obvious. She suffered a non progressive injury to some part of the ventilatory system when she was born [she needed resuscitation, etc..], has depressed ventilation as an adult and thus is at risk for [most likely] acute on chronic hypercapnia causing mental confusion and her ventilation needs rescuing [as it did at birth] when the system becomes overwhelmed after infection or viruses causing poor physical condition [involuntary loss of weight, dehydration, muscle wasting, etc…-all of which were also missed by her doctors- you do not see what you are not looking for, I guess..]
Paula understood that she had some kind of medical syndrome and she knew that no one would understand what needed to be done. She knew that no one realized the extent of autobiographical memory loss she was experiencing and she could not explain because of her cognitive impairment.
Paula and I think that psychiatric and neurological and internal medicine wards and outpatient clinics should become specialists in clinical medical investigation and research and treatments of the myriad syndromes of metabolic encephalopathy [mental confusion], because that is what serious mental illness is likely to be.
That way the overworked Emergency Department would be able to refer these cases to a multidisciplinary team of doctors who will take as much time as is necessary, to uncover the underlying pathophysiology [anywhere in the body] causing secondary effects in the brain. And they would find supportive medical treatments to restore mental functioning even if they could not fix the primary problem. [in Paula’s case, her depressed breathing is permanent, so she will need to be followed especially after illness, infection, inflammation, blood loss, injury, etc…in order to quickly restore her mental functioning when her ventilatory system becomes overwhelmed.
If her mental state is restored [even if antibiotics and home ventilation is needed], then she will be able to lead a normal life. Whatever the nature of Paula’s ventilatory problem is, it seems to be a non progressive injury, so she can live a normal life with occasional medical support.
That is much better than being depressed and insane for decades, if not given the correct treatment, don’t you think?
Just ask Paula herself; she will tell you that she is active and happy and smart [to her normal baseline] , despite her hidden broken breathing, as she calls it. And she has recovered better than a lot of people with this syndrome, so you see…it’s not so bad, as long as complete cognitive recovery is restored, of course. Otherwise, it is a nightmare. Ask Paula, ….she knows,…. she remembers . No one should be left to suffer that way….