CDC Warns of Increased Ivermectin Overdoses

The US Centers for Disease Control and Prevention (CDC) is warning of an increase in cases of ivermectin overdose due to people self-prescribing the drug in an effort to prevent or treat COVID-19 (1). Ivermectin is used to treat river blindness and intestinal roundworm infection in humans and to de-worm pets and livestock. 

A study published earlier this year showed that ivermectin killed SARS-CoV-2 in cells in vitro. The authors proposed that the medication be investigated as a cheap and easily available treatment for COVID-19. However, subsequent studies have failed to find any benefit in humans (3).

In a new communication to its Health Alert Network, the CDC says cases of overdose and misuse are rising (1). More than 88,000 prescriptions were written for the drug ivermectin in the week ending August 13, an increase of 2400% over the weekly average prior to the COVID-19 pandemic (Figure 1).

Figure 1. Ivermectin prescriptions by week (from CDC, reference 1).

Unfortunately, the signs of overdose are nonspecific but can include gastrointestinal symptoms (nausea, vomiting, and diarrhea), hypotension and altered mental status (change in consciousness, confusion, hallucinations, seizures, coma).

The CDC is asking doctors to alert their patients to the risks of ivermectin, particularly ivermectin products intended for veterinary use. Physicians might suspect ivermectin in a patient with unexplained symptoms and are encouraged to contact their local poison control for assistance.

References

1. CDC. Rapid Increase in Ivermectin Prescriptions and Reports of Severe Illness Associated with Use of Products Containing Ivermectin to Prevent or Treat COVID-19. August 26, 2021. Available at: https://emergency.cdc.gov/han/2021/han00449.asp (accessed 8/27/21).
2. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020 Jun;178:104787. [CrossRef] [PubMed]
3. Popp M, Stegemann M, Metzendorf MI, Gould S, Kranke P, Meybohm P, Skoetz N, Weibel S. Ivermectin for preventing and treating COVID-19. Cochrane Database Syst Rev. 2021 Jul 28;7:CD015017. [CrossRef] [PubMed]

Cite as: Robbins RA. CDC Warns of Increased Ivermectin Overdoses. Southwest J Pulm Crit Care. 2021;23(2):62-3. doi: https://doi.org/10.13175/swjpcc038-21 PDF 

CDC Releases Ventilator-Associated Events Criteria

A new term has been coined by the CDC, ventilator-associated events (VAEs) (1). In 2011, the CDC convened a working group composed of members of several stakeholder organizations to address the limitations of the definition of ventilator-associated pneumonia (VAP) definition (2). The organizations represented in the Working Group include: the Critical Care Societies Collaborative (the American Association of Critical-Care Nurses, the American College of Chest Physicians, the American Thoracic Society, and the Society for Critical Care Medicine); the American Association for Respiratory Care; the Association of Professionals in Infection Control and Epidemiology; the Council of State and Territorial Epidemiologists; the Healthcare Infection Control Practices Advisory Committee’s Surveillance Working Group; the Infectious Diseases Society of America; and the Society for Healthcare Epidemiology of America.

VAEs are defined by an increase oxygen (>0.2 in FiO2) or positive end-expiratory pressure (PEEP) (≥3 cm H2O), after a previous stable baseline of at least 2 days. There are three definition tiers within the VAE algorithm: 1) Ventilator-Associated Condition (VAC); 2) Infection-related Ventilator-Associated Complication (IVAC); and 3) Possible VAP (PVAP) (2). There are also many other criteria to classify a VAE into the CDC’s tiers which are omitted for brevity. These definitions have been implemented in the National Healthcare Safety Network (NHSN) and according to the CDC are easily implemented, can make use of electronic health record systems to automate event detection, and identify events that are clinically important and associated with outcomes such as ICU and hospital length of stay and mortality. According to the CDC most VACs are due to pneumonia, ARDS, atelectasis, and pulmonary edema which “are significant clinical conditions that may be preventable”.

The CDC says "the VAE definition algorithm is for use in surveillance; it is not a clinical definition algorithm and is not intended for use in the clinical management of patients”. Based on the experience with the hospital acquired infections program this seems unlikely. What seems more likely is that hospitals will be measured on VAE rates with financial or public relations consequences shortly to follow.

The best evidence suggests that the VAE concept is not useful for guiding clinical decisions in the moment (1). Its performance characteristics as a screening test appear to be terrible, with poor sensitivity (~32%) for detecting VAP in the one of the only prospective studies. This is because clinically insignificant fluctuations in oxygenation/PEEP status are often recorded as VAEs, diluting signal with noise. Numerous retrospective reviews supporting the VAE concept listed on CDC's website strongly link VAEs with morbidity and mortality. However, these observations could be true of many events and may be very different from showing that a prospective (intervention-based) approach is helpful. Pulmonologist Dr. Richard Wunderink from Northwestern commented that “the central hypothesis of the VAE criteria—that VAP and other potentially preventable complications of mechanical ventilation can consistently be detected by worsening gas exchange—is clearly not true”.

The problems with VAE appear much the same as the problems with VAP. Neither is strongly evidence-based and neither has been shown to be helpful in patient care. Furthermore, it might be possible to “game” the numbers by adjusting PEEP, expiratory time, and FiO2 within the defined limits.

Richard A. Robbins, MD

Editor, SWJPCC

References

1. Pulm/CCM. What are ventilator-associated events (and why should you care)? Available at: http://pulmccm.org/main/2014/review-articles/ventilator-associated-events-care/?utm_source=Email+Updates+from+PulmCCM&utm_campaign=b1ee59472e-USP_mar_24_2014&utm_medium=email&utm_term=0_e9d9e09c7c-b1ee59472e-312029025 (accessed 1/24/17).
2. CDC. Ventilator-associated event (VAE). January 2017. Available at: https://www.cdc.gov/nhsn/pdfs/pscManual/10-VAE_FINAL.pdf (accessed 1/24/17).

Cite as: Robbins RA. CDC releases ventilator-associated events criteria. Southwest J Pulm Crit Care. 2017:14(1):40-1. doi: https://doi.org/10.13175/swjpcc009-17 PDF 

Most Drug Overdose Deaths from Nonprescription Opioids

The Centers for Disease Control (CDC) is reporting in Morbidity and Mortality Weekly that the number of people dying from an opioid overdose rose 15.5% from 2014 to 2015, but the increase had little to do with prescription painkillers such as oxycodone or hydrocodone (1). Roughly 52,000 people died from drug overdoses in 2015 and of those deaths 33,091 involved an opioid. The increases in “death rates were driven by synthetic opioids other than methadone (72.2%), most likely illicitly-manufactured fentanyl, and heroin (20.6%)”. Deaths from methadone, which is usually prescribed by physicians, decreased 9.1%.

The largest increase in deaths occurred in the South and Northeast with 3% and 24% increases in deaths from synthetic opioids from 2014 to 2015. In the Midwest and West, there were more modest 17% and 9% increases during the same period. States in the Southwest with “good” to “excellent” reporting included Colorado, Nevada, and New Mexico which showed 33%, 14% and 30% decreases respectively.

Earlier this year, CDC Director Tom Frieden, MD, MPH, said "The prescription overdose epidemic is doctor-driven…It can be reversed in part by doctors' actions” (2). That characterization has rung in some physicians' ears as blame for the entire opioid crisis, including deaths from heroin and illegal fentanyl. The data in the present article suggests that characterization is inaccurate and that efforts by a number of State Boards to limit physician opioid prescribing may be marginally or non-effective in reducing overdose deaths.

Richard A. Robbins, MD

Editor, SWJPCC

References

1. Rudd RA, Seth P, David F, Scholl L. Increases in drug and opioid-involved overdose deaths - United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016 Dec 16;65. Published on-line. [CrossRef]
2. Lowes R. CDC issues opioid guidelines for 'doctor-driven' epidemic. Medscape. March 15, 2016. Available at: http://www.medscape.com/viewarticle/860452 (accessed 12/21/16).

Cite as: Robbins RA. Most drug overdose deaths from nonprescription opioids. Southwest J Pulm Crit Care. 2016;13(6):316. doi: https://doi.org/10.13175/swjpcc145-16 PDF

VAP Rates Unchanged

In a research letter to JAMA Metersky and colleagues (1) report that ventilator-associated pneumonia (VAP) rates have remained near 10% since 2005. The authors reviewed Medicare Patient Safety Monitoring System (MPSMS) data on a representative sample of more than 86,000 critically ill patients treated at 1330 US hospitals between 2005 and 2013. To meet a diagnosis of VAP patients were required to have at least 2 days' ventilation in intensive care units; a chest radiograph with a new finding suggesting pneumonia; a physician diagnosis of pneumonia; and an order for antibiotics. VAP incidence was 10.8% (95% confidence interval, 7.4% - 14.4%) during 2005 to 2006 and 9.7% (95% confidence interval, 5.1% - 14.9%) during 2012 to 2013.

In contrast, data from the CDC's National Healthcare Safety Network (NHSN) have shown declines in VAP rates of 71% and 62% in medical and surgical intensive care units, respectively, between 2006 and 2012 (2,3). "The most likely explanation for the discrepancy is thought to be bias in reporting to CDC by the hospitals," Dr. Metersky told Medscape Medical News (4). Dr. Charles S. Dela Cruz at Yale agrees. "Strict and varying VAP measure definitions and the hospital reporting mechanisms possibly contributed to the differences in rates," he said.

VAP has no standard definition and its diagnosis has considerable clinical variability. Other than removing the endotracheal tube as quickly as possible, VAP prevention guidelines are non- or weakly evidence-based (5). Furthermore, financial incentives from CMS for low VAP rates may have contributed to the bias in reporting (6).

Richard A. Robbins, MD

Editor, SWJPCC

References

1. Metersky ML, Wang Y, Klompas M, Eckenrode S, Bakullari A, Eldridge N. Trend in ventilator-associated pneumonia rates between 2005 and 2013. JAMA. 2016 Nov 11. [Epub ahead of print] [CrossRef] [PubMed]
2. Edwards JR, Peterson KD, Andrus ML, et al; NHSN Facilities. National Healthcare Safety Network (NHSN) Report, data summary for 2006, issued June 2007. Am J Infect Control. 2007;35(5):290-301. [CrossRef] [PubMed]
3. Dudeck MA, Weiner LM, Allen-Bridson K, et al. National Healthcare Safety Network (NHSN) report, data summary for 2012, device-associated module. Am J Infect Control. 2013;41(12):1148-66. [CrossRef] [PubMed]
4. Swift D. No drop in VAP rates, study contends. Medscape Medical News. November 21, 2016. Available at: http://www.medscape.com/viewarticle/872157?nlid=110853_3464&src=WNL_mdplsfeat_161129_mscpedit_ccmd&uac=9273DT&spon=32&impID=1243721&faf=1 (accessed 12/2/16).
5. Padrnos L, Bui T, Pattee JJ, Whitmore EJ, Iqbal M, Lee S, Singarajah CU, Robbins RA. Analysis of overall level of evidence behind the Institute of Healthcare Improvement ventilator-associated pneumonia guidelines. Southwest J Pulm Crit Care 2011;3:40-8.
6. Cassidy A. Medicare's hospital-acquired condition reduction program. Health Affairs. August 6, 2015. Available at: http://www.healthaffairs.org/healthpolicybriefs/brief.php?brief_id=142  (accessed 12/2/16).

Cite as: Robbins RA. VAP rates unchanged. Southwest J Pulm Crit Care. 2016;13(6):288-9. doi: https://doi.org/10.13175/swjpcc134-16 PDF