June 2015 Critical Care Case of the Month: Just Ask the Nurse

Robert A. Raschke, MD

Banner University Medical Center

Phoenix, AZ

 History of Present Illness

A 61-year-old police officer had just finished delivering a speech at a law enforcement conference in Phoenix when he briefly complained of chest pain or chest tingling before lapsing into a mute state. He became diaphoretic cyanotic, and vomited. Emergency medical services was called. They noted a blood pressure of 80/50 mm Hg, a pulse of 45, temperature of 95º F, a respiratory rate of 12, and widely dilated pupils. He was transported to the emergency room.

PMH, SH, FH, Medications

Unknown.

Physical Examination

Vital signs: blood pressure 120/75 mm Hg by oscillometric thigh cuff, pulse 43 and irregular, temperature 96º F, respiratory rate 10, SpO2 96% on O2 @ 5L/min by nasal cannula

Neck: No JVD.

Lungs: Poor inspiratory effort

Heart: Irregular rhythm without a murmur

Neurological:

• Delirious – mute – won’t obey commands or track with his eyes
• Pupils 3 mm reactive
• Withdrew 3 extremities to nail bed pressure – he will defend his left arm with his right arm

He suddenly became asystolic and cardiopulmonary resuscitation was begun. After about a minute a femoral pulse could be felt.

Which of the following are indicated at this time? (Click on the correct answer to proceed to the second of five panels)

1. Arterial blood gas
2. Chest x-ray
3. Electrocardiogram
4. Electrolytes
5. All of the above

Reference as: Raschke RA. June 2015 critical care case of the month: just ask the nurse. Southwest J Pulm Crit Care. 2015;10(6):323-9. doi: http://dx.doi.org/10.13175/swjpcc077-15 PDF

Acute Pregabalin Withdrawal: A Case Report and Review of the Literature

Jaclyn A. Barrett, PharmD

Lindsay M. Kittler, PharmD, BCPS

Clement Singarajah, MD, FCCP

Phoenix VA Medical Center

Phoenix, AZ 85012

Abstract

Objective: Pregabalin is a commonly prescribed GABA analog most commonly used for the treatment of neuralgia. Recently, case reports on pregabalin have been published describing episodes that may be associated with withdrawal-like symptoms after extended or aggressive therapy. This report describes a case in which long term exposure of high dose pregabalin may have resulted in acute withdrawal, and outlines the subsequent medical management of these symptoms.

Case Summary: A 61-year-old male presenting with severe agitation presumed to be withdrawal from long term and high dose exposure to pregabalin. Medical management included the use of haloperidol, diphenhydramine, lorazepam and the addition of clonidine over the course of several days for the pharmacological management of withdrawal symptoms.

Discussion: Although case reports are available to guide clinicians in the recognition of acute pregabalin withdrawal, definitive evidence on how best to treat these patients remains severely limited. With an increase in the prescribing practices of pregabalin, insight into the acute management by fellow clinicians is further needed.

Conclusion: Caution must be practiced when prescribing and educating patients on the use of pregabalin to prevent associated withdrawal-like symptoms. In addition, documentation by the medical community on methods utilized to treat pregabalin withdrawal syndromes remains crucial for the advancement of patient care. Benzodiazepines and clonidine are the current therapies that have been documented as potentially effective treatment modalities at this time.

Introduction

Pregabalin is a gamma-aminobutyric acid (GABA) analogue currently FDA labeled for diabetic peripheral neuropathy, fibromyalgia, neuropathic pain, partial seizures and postherpetic neuralgia, and is used off-label in various psychiatric disorders. It is proposed that pregabalin binds strongly to an alpha-2-delta subunit on voltage gated calcium channels within the central nervous system. Pro-nociceptive neurotransmitter release that is dependent upon calcium is thereby reduced. Additional mechanisms for pregabalin’s efficacy may be comprised of noradrenergic and serotonergic pathways involved in pain transmission (1).

Case Presentation

We report the case of a 61-year-old man who presented with sudden and severe withdrawal like symptoms characterized by family as extreme agitation with combative behavior, diaphoresis, tachycardia, hypertension, tremors, and incontinent diarrhea. Reportedly, prior to admission, the patient had become increasingly somnolent with multiple falls and psychotic behavior similar to one responding to internal stimuli. A review of his home prescription vials revealed a presumed, excessive consumption of immediate-release oxycodone and pregabalin over the last few days and up to a week. His past medical history included chronic obstructive pulmonary disease, osteoarthritis, neuropathic pain, hypothyroidism, hyperlipidemia, anxiety and major depressive disorder. A thyroid stimulating hormone level was checked upon admission and was within normal limits with no other metabolic explanation for his symptoms identified. The patient did present with a prior medical history of opioid abuse with previous enrollments in substance abuse programs, but compliance with his current pain management contract was confirmed using the state’s controlled substance prescription monitoring program database.

Upon admission through the emergency room, the patient remained severely agitated with increasingly combative behavior despite the administration of the antipsychotic, haloperidol. Without relief, the benzodiazepine, lorazepam, was administered resulting in a paradoxical effect causing increased aggression and agitation and thus discontinued. Implementation of scheduled hydromorphone was administered for acute opioid withdrawal but similarly provided minimal symptom abatement yet, maintained adequate analgesia. After medication review and reconciliation, the patient was currently on a prescribed, scheduled dose of pregabalin 300 mg twice daily over the course of approximately eight months for the treatment of neuropathic pain. Although initially concerned for potential overdose, all symptoms upon presentation were deemed to be consistent with a withdrawal syndrome, pregabalin being the most likely culprit given lack of symptom abatement with the use of benzodiazepines and opioids with no other likely cause upon review of his home medications and laboratory data.

After transferring to the Intensive Care Unit, the patient was further treated with intravenous haloperidol 10 mg and diphenhydramine 50 mg every 4 hours providing only minimal relief while protecting both the safety of the patient and staff. Management of acute pregabalin withdrawal was further complicated by the inability to provide pregabalin orally, due to disorientation and the physical inability to maintain placement of a nasogastric tube. Sedation and mechanical ventilation was not an option as the patient’s established wishes were a Do Not Intubate (DNI) status. Sublingual clonidine 0.1 mg was later administered every four hours and up to every hour if needed, in addition to the haloperidol and diphenhydramine. The anti-adrenergic agent clonidine was most effective in providing withdrawal symptom reduction, and the haloperidol and diphenhydramine were rapidly tapered off. In addition, our patient developed urinary retention necessitating the discontinuation of diphenhydramine. The discontinuation of diphenhydramine lead to a retrial of lorazepam which provided effective relief for the management of his later course agitation with no paradoxical agitation observed.

This case demonstrates an issue of common occurrence, where a patient is withdrawing clinically from a drug with often non-specific symptom manifestations. Further confounding this clinical presentation, several possible sources of drug withdrawal required the medical team to address each drug individually in order to identify the offending agent. With this in mind, withdrawal from pregabalin, although not often considered a drug of abuse or associated with intense withdrawal, may only be identified by ruling out other suspected agents, such as in this patient scenario.

Discussion

In review of current literature, case reports have arisen that describe symptoms of withdrawal from abrupt discontinuation of pregabalin. Several case reports describe a withdrawal-like syndrome to include signs and symptoms such as agitation, anxiety, confusion, gastrointestinal distress, tachycardia and palpitations, similar to benzodiazepine withdrawal (2-4).

Oaklander and Buchbinder (2) report a case involving an 80-year-old woman prescribed pregabalin 125 mg three times daily for 49 weeks as treatment for postherpetic neuralgia. Within 36 hours of abrupt discontinuation, the patient developed severe nausea, headache, imbalance, delirium and anorexia. Over the course of several weeks, the patient developed hemodynamic instability and continued to experience episodes of ataxia for a six month duration.

Another report by Karosin et al. (3), describes a 47-year-old male who reportedly consumed a total daily dose of 7,500 mg of pregabalin daily in addition to alcohol and cocaine abuse. In a failed attempt to wean off pregabalin the patient developed what was described to be vegetative withdrawal symptoms, sweating, restlessness, hypertension, tremor and pregabalin cravings. Upon admission, the patient received treatment with benzodiazepines without relief and a slow taper of pregabalin was initiated yet, cravings continued which ultimately resulted in the patients continued abuse of this GABA analog.

In a case report by Norgaard et al. (4), a 38 year-old man was self-administering 8.4 g pregabalin daily and within 36 hours of cessation of pregabalin developed auditory hallucinations and suicidal ideation in addition to sweating, anxiety and tachycardia. Pregabalin was reinitiated at 600 mg per day in addition to supplemental chlordiazepoxide and quetiapine. Acute symptoms resolved within 48 hours yet the symptoms of psychosis remained present until several weeks after discontinuation.

In addition, case reports regarding gabapentin withdrawal have been published to include similar clinical presentations. Gabapentin, another GABA analog, is FDA approved for the treatment epilepsy, neuralgia and restless leg syndrome, and is widely used in the prophylaxis of migraines, headaches and ethanol withdrawal (5). It is hypothesized that the mechanism of withdrawal is associated with increased activity of the enzyme responsible for producing GABA, similar to the mechanism behind ethanol and benzodiazepine withdrawal (6).

Hellwig et al. (6) and Mah et al. (7), describe similar symptoms of irritability, confusion and agitation unrelieved by the administration of benzodiazepines. Gabapentin was identified as the causative agent of withdrawal after reinstatement of the GABA analog provided relief in both case reports. In addition to drug related factors, potential patient related risk factors that may increase the susceptibility of withdrawal include advanced age and history of psychiatric illness.

Currently, pregabalin is a schedule V controlled substance due to its potential for addiction and abuse (8). According to the manufacturer, there are no current recommendations for the management of an acute drug withdrawal syndrome from pregabalin, yet current practice suggests that a gradual taper, generally recommended with all extended controlled substance therapy, may be warranted. This report suggests that clonidine may be an effective agent in the management of acute agitation associated with pregabalin withdrawal. Literature has historically supported the use of clonidine in a variety of drug withdrawal syndromes owing to its known central alpha 2 agonist activity, but remains underutilized amongst providers in current practice (9-11). Another alternative to consider is dexmedetomidine, a centrally acting, alpha 2 adrenoceptor agonist which has demonstrated its efficacy as an adjunctive treatment for refractory alcohol withdrawal (12). Due to concomitant hypertension and institutional cost, dexmedetomidine was considered second line in the event that clonidine was ineffective for our patient.

Although case reports are available to guide clinicians in the recognition of acute pregabalin withdrawal, definitive evidence on how best to treat these patients remains severely limited. With an increase in the prescribing practices of pregabalin, insight into the acute management by fellow clinicians is further needed to provide evidence-based guidance in the management of these patients. As for our clinical case of acute pregabalin withdrawal in the presence of hallucinatory features, we advise against the use of benzodiazepines due to the risks of paradoxical agitation, and would suggest withholding their use until the latter stages of withdrawal. If possible, as was not in our case, initiating a pregabalin taper would ideally preferred. We also propose that the use of clonidine has clinically shown, as demonstrated in this patient case, to provide appropriate supportive treatment for the management of acute pregabalin withdrawal.

References

1. Pregabalin. DrugPoint Summary. Micromedex. Truven Health Analytics, Inc. Greenwood Village, CO. Available at: http://www.micromedexsolutions.com. Accessed April 26, 2014.
2. Oaklander AL, Buchbinder BR. Pregabalin-withdrawal encephalopathy and splenial edema: a link to high-altitude sickness? Ann Neurol. 2005;58(2):309-12. [CrossRef] [PubMed]
3. Karosin C, Kofler M, Mayr A, et al: Pregabalin: A treatment option for dystonia? Neurol Sci. 2012;33(2):351-4. [CrossRef] [PubMed]
4. Nordgaard J, Jurgens G. A case of pregabalin abuse. Clin Toxicol. 2013;51(4):320
5. Gold Standard, Inc. Gabapentin. Clinical Pharmacology [database online]. Available at: http://www.clinicalpharmacology-ip.com/Forms/drugoptions.aspx?cpnum=271&n=Gabapentin&t=0 Accessed: 5/19/2015.
6. Hellwig TR, Hammerquist R, Termaat J. Withdrawal symptoms after gabapentin discontinuation. Am J Health Syst Pharm. 2010;67:910-2. [CrossRef] [PubMed]
7. Mah L, Hart M. Gabapentin withdrawal: case report in an older adult and review of the literature. J Am Geriatr Soc. 2013;61(9):1635-7. [CrossRef] [PubMed]
8. LYRICA® (pregabalin) CV Safety Info. Available at: http://www.lyrica.com. Accessed April 27, 2014.
9. Baumgartner GR, Rowen RC. Clonidine vs chlordiazepoxide in the management of acute alcohol withdrawal syndrome. Arch Intern Med. 1987;147:1223-6. [CrossRef] [PubMed]
10. Baumgartner GR, Rown RC. Transdermal clonidine versus chlordiazepoxide in alcohol withdrawal: a randomized, controlled clinical trial. South Med J. 1991;84:312-21. [CrossRef] [PubMed]
11. Robinson BJ, Robinson GM, Mailing TJB, Johnson RH. Is clonidine useful in the treatment of alcohol withdrawal? Alcohol Clin Exp Res. 1989;13:95-8. [CrossRef] [PubMed]
12. Tolonen J, Rossinen J, Alho H, Harjola VP. Dexmedetomidine in addition to benzodiazepine-based sedation in patients with alcohol withdrawal delirium. Eur J Emerg Med. 2013;20:425. [CrossRef] [PubMed]

Reference as: Barrett JA, Kittler LM, Singarajah C. Acute pregabalin withdrawal: a case report and review of the literature. Southwest J Pulm Crit Care. 2015;10(5):306-10. doi: http://dx.doi.org/10.13175/swjpcc059-15. PDF

Organ Failure in Acute Pancreatitis and Its Impact on Outcome in Critical Care

Namrata Maheshwari, MD, IDCCM

Arun Kumar, MD 

Zafar A Iqbal, MD

Amit K Mandal, DNB,DTCD

Abhishek Vyas, MBBS

Jai D Wig, MS

Department of Critical Care Medicine and Pulmonology

Fortis Hospital 

Mohali, Punjab, 160062

India 

Abstract

The most important determinant of mortality in acute pancreatitis is organ failure (OF). The aim of this prospective observational study was to determine the incidence of organ failure in acute pancreatitis and its relation with the extent of necrosis and outcome. Sixty-one patients were divided into 3 groups: no organ failure (NOF), transient organ failure (< 48 hrs) (TOF) or persistent organ failure (> 48 hrs) (POF). Of 61 patients, 30 patients had no organ failure (49.1%), while 11 patients (18%) had TOF and 20 patients (32.7%) had POF. The mean age was 46.5 yrs with male predominance. Pulmonary and renal failures were the most common (32%), followed by CVS (cardiovascular system), coagulation system and CNS (central nervous system). Fourteen (46.4%) patients had one or two OF, 17 (56.6%) had more than two OF. There were no deaths in patients with up to two organ failures but a 70% (7) death rate in those with three organ involvement, 80% (4) with four and 100% with five OF. The percentage of pancreatic necrosis was evaluated for its relationship with organ failure. In the NOF group 19 (63.3%) patients had no necrosis, as compared to 11 patients with necrosis in TOF and POF groups (35.4%). Out of 61 patients, 13 patients died. All 13 patients who expired belonged to the POF group (p <.001). Early persisting and deteriorating organ failure had the worst outcomes. There was an increase in mortality with an increasing number of organs involved. The extent of necrosis was directly related with incidence of organ failure.

Introduction

Acute pancreatitis (AP) is characterized by a variable clinical course varying from a mild self-limited disease (80-90%) to a clinically severe acute pancreatitis (SAP) in 10-20% (1-4). Despite advances in knowledge and treatment of AP, the identification of patients with clinically severe disease on admission remains difficult (1) and the mortality in several series continues to be around 20% (2,5). 

The factors responsible for high mortality in patients with SAP are organ failure (OF) and pancreatic necrosis (6,7). The reported incidence of OF in SAP varies from 28-76 % (5,8,9). The occurrence of organ dysfunction and progressive organ failure has a major impact on outcome. Many patients who succumb to AP within the first two weeks of disease onset do so from overwhelming multiorgan failure (10,11). Other studies have also reported that prognosis deteriorated with an increase in number of organs involved (12,13). Banks and Freeman (14) studied the correlation between mortality and organ failure in patients with acute pancreatitis and documented a median mortality of 3% in patients with single organ failure and 47% in patients with multisystem organ failure. Another study documented that the overall mortality (47.8%) correlated with the number of organs failing (6). The definition of multiorgan failure is broad and encompasses transient to persistent or severe multiorgan failure that requires critical care support (15). Patients with persistent organ failure have a higher mortality as compared to patients where organ failure resolves (16). Johnson and Hial (17) showed that patients with OF that resolved within 48 hours(transient) have a low risk of complications and death in comparison to patients who have persistent organ failure(OF persisting for 3 or more days) and have a greater than one in three risk of fatal outcome. Information regarding the prediction of persistent organ failure in patients with acute pancreatitis is not available (18).

One of the factors linked to the development of OF is the extent of pancreatic necrosis. Some workers have found a correlation between the extent of necrosis and OF (19). The question of the relationship between infected necrosis and OF remains unsettled. There is no consistency in the literature on whether organ failure or infected necrosis is the main determinant of severity in acute pancreatitis. The aim of study was to study the occurrence of organ failure in acute pancreatitis and determine the influence of organ failure on mortality in patients with acute pancreatitis.

Materials and Methods

This study was a prospective study under taken during 18 months (December 2011 to May 2013) in the Departments of Gastroenterology, General Surgery and Medical Intensive Care Unit in Fortis Hospital, Mohali, Punjab, a 260 bedded multispecialty tertiary care hospital in Northern India.

The study sample included all consecutive patients diagnosed with acute pancreatitis referred to Gastroenterology or General surgery units fulfilling the inclusion and exclusion criteria. All the patients were assessed for demographic profile and detailed symptom profile. After a detailed clinical examination relevant investigations were repeated as and when required. Patients were monitored for the presence and severity of organ failure every day during the first week, subsequent local complications, subsequent episodes of sepsis, and death or other outcomes during the same hospital admission.

Organ failure was defined as per modified multiple organ failure score (MMOFS). Transient organ failure was defined as organ failure present for less than 48 hours, and persistent organ failure was recorded when organ failure was present for more than 48 hours, where day 0 was the day of entry to the study and day one started at 8.00am on the day after entry. The course in hospital and final outcome was recorded. Cross tabulations were made with outcome, in particular with mortality.

Statistical Analysis. The data are presented as mean ± SD or median and interquartile range, as appropriate. The Mann- Whitney U-test was used for statistical analysis of skewed continuous variables and ordered categorical variables. For normally distributed data The t-test was applied. Pearson χ2 test or Fisher’s exact test was used for analysis of categorical variables with two categories. A p value of <0.05 was considered to indicate statistical significance. All calculations were performed using SPSS® version 15 (Statistical Packages for the Social Sciences, Chicago, IL).

Results

The study was comprised of 61 patients who met the inclusion criteria with diagnosis of acute pancreatitis. The study group was further divided as per organ failure into three groups:

• No organ failure (NOF)
• Transient organ failure ( < 48 hrs) (TOF)
• Persistent organ failure ( > 48 hrs) (POF)

Demographic Distribution. The mean age of the patients was 46.5 years. The majority of patients were in the age group of 30-50 years. In this study the youngest patient was 17 years old and oldest was 87 years old (Figure 1).  

Figure 1. Age distribution with increased number of organs involvement.

The male to female ratio was found to be 2.4:1 (Figure 2).

Figure 2. Sex distribution.

Male predominance was found in all groups (53.3 %, 81.8%, and 90 % in the no organ, transient and persistent organ failure group respectively).

Comorbid Conditions. A majority of the patients (38) in our study group had no associated comorbid conditions  while 23 patients (37.8%) had a previous comorbid condition. Hypertension was the most common comorbid condition, seen in almost 31 % of the patients at the time of admission. Type 2 diabetes was the second most common condition noted in 24.6%, followed by hypothyroidism (4.9%), asthma, depression, cardiomyopathy and Guillain-Barré syndrome in 1.6% each (Table 1).  

Table 1. Comorbid conditions associated in our study group.

 

We could not find any association between co morbidities and mortality as 9 (62.9%) deaths occurred in the no comorbidity group as compared to 4 (30.8%) deaths in the co morbidities group (p=0.880).

Etiology. The most common etiologies of pancreatitis in our study group were alcohol and gall stones (n=24, 39% each) (Table 2).

Table 2. Etiology of acute pancreatitis.

Other causes were idiopathic (n=10, 17%), hypertriglyceridemia (n=2, 3%) and pancreatic divisum (n=1, 2%).

Percentage of Necrosis and Organ Failure. The percentage of necrosis on radiological imaging (in 46 patients) was evaluated for its relationship with organ failure. In the NOF group 19 (63.3%) patients had no necrosis (0%), 4 (13.3%) patients had <30% necrosis, 1 (3.3%) had 30-50% and 4 (13.3%) had >50% necrosis (Figure 3).

Figure 3. Relation between organ failure and pancreatic necrosis.

In the TOF group, 4 (36.4%) patients revealed no necrosis on contrast-enhanced computerized tomography (CECT) of the abdomen, <30% necrosis in 2 (18.2%) patients, 30-50% necrosis in 3 (27.3%) and >50% in 1 (9.1%) patient (Figure 3).

In POF group no necrosis was detected in 3 (15%) patients, <30 % in 2 (10%), 30-50% in 1 (5%) and >50% in 2 (10%) patients. The relationship between the amount of necrosis was directly related with incidence of organ failure and this correlation was found to be statistically significant (Figure 3).

MMOFS and Mortality. We divided our study in 3 groups, no organ failure, transient (<48 hrs) and persistent (>48 hrs) organ failure to understand the nature and dynamics of organ failure. Groups were further divided in early onset (<7days), late onset (>7days). Organ failure was calculated by the Modified multiorgan failure score (MMOFS). Daily MMOFS was calculated in all patients up to 7 days. MMOFS difference was calculated by MMOFS 7 (MMOFS at day 7) – MMOFS 1 (at the time of admission). On the basis of MMOFS difference groups were further divided into same (if difference was 0), improving (if deference was negative value), or deteriorating (if deference was a positive value) groups (Figure 4).

Figure 4. Comparison of outcome with MMOFS difference.

MMOFS difference was found to be highly significantly (ANOVA, p<0.001 each) correlated with organ failures and outcome. In our study no deaths occurred in the transient OF groups (early transient, late transient and transient deteriorating). We attributed this to the dynamics that transient OF could resolve with treatment and had a better outcome than persistent OF. Among the 13 deaths reported in our study, 46.2 % were in the early (<7 days) OF group compared to the late (>7 days) OF group (20%).

Organ Involvement. Pulmonary and renal failures were the most common organ involvements noted among our study group (32% each). This was followed by cardiovascular system (22%), coagulation system (8%) and central nervous system (6%) (Figure 5).

Figure 5. Organ failure by system.

Organ involvement and mortality. Fourteen (46.4%) patients had one or two OF and 17 (56.6%) had more than two OF (table 3). Comparison of the number of organ failures to mortality was statically significant (p<0.001) (Figure 6).

Figure 6. Outcome in patients with increasing organ involvement.

We found that there was an increase in incidence of mortality with an increase in the number of organs involved. There were no deaths in patients with up to two organ failures; it increased with increasing number of organs involved (Table 3).

Table 3. Organ failure and mortality.

The mortality rate was 70% (n=7) with three organ involvement, 80 % (n=4) with four and 100% with five OF.

Discussion

Severe acute pancreatitis is a systemic disease and characterized by acute onset and rapid progression, with a high incidence of complications and serious morbidity (20). An international multidisciplinary classification of acute pancreatitis severity is based on local and systemic determinants of severity. The local determinants relate to presence of pancreatic necrosis, and whether the necrosis is infected or sterile. The systemic determinants relate to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of both infected pancreatic necrosis and persistent organ failure has a greater impact on severity than either determinant alone. Based on these principles, the severity is classified as mild, moderate, severe or critical (21).The three most common systems involved are renal, lung, and cardiovascular system. Respiratory complications are frequent in acute pancreatitis and respiratory dysfunction is a major component of multiple organ dysfunction syndrome (22,23). In a population based study, 15.05% of patients with AP had a diagnosis of acute renal failure (24).

The present study showed that the difference in age was not significantly different between the groups. There are some studies which showed an association between advancing age as a predictor of organ failure and mortality. Wig et al. (6) studied 161 patients and concluded that age of the patients was a risk factor for multiple organ failure. Li et al. (25) studied 181 patients with SAP and found a correlation of age with OF (<.001). Frey et al²⁶ also showed that the number of complications was positively correlated with the age of patients. Older age and number of complications were strong predictors of organ failure among patients with SAP. Though we recorded a higher incidence of organ failures and mortality in a younger age group of 40-45, the difference was attributed to a small number of patients above 65 years in our study as compared to studies done in the western world.

The bedside index for severity in acute pancreatitis (BISAP) score represents a simple way to identify patients at risk for increased mortality and the development of intermediate markers of severity within 24 hours of presentation. In our series the BISAP score was significantly associated (p<.001) with organ failure as well as survival (p<.001). We found 9 out of 13 deaths in the >3 score group and four deaths at a BISAP score of 2 as compared to zero mortality in the BISAP score 1 and 0 group. Kim et al. (27) also compared BISAP, the serum procalcitonin (PCT), and other multifactorial scoring systems simultaneously, concluded that BISAP is more accurate for predicting the severity of acute pancreatitis than the serum procalcitonin, APACHE-II, Glasgow, and modified CT severity index (MCTSI) scores. Chen et al. (28) evaluated the accuracy of BISAP in predicting the severity and prognosis of acute pancreatitis (AP) in 497 Chinese patients. They conclude that BISAP score is valuable in predicting the severity of AP and prognoses of SAP in Chinese patients.

Contrast enhanced computed tomography (CECT) is considered the gold standard for the diagnosis of pancreatic necrosis and peripancreatic collections. CT assessment correlates with the clinical course of the disease and recognized variables of disease severity. We ordered CECT in all patients on the second or third day after admission rather than at the time of admission. Additional contrast-enhanced CT scans were ordered at intervals during the hospitalization to detect and monitor the course of intra-abdominal complications of acute pancreatitis, such as the development of organized necrosis, pseudocysts, and vascular complications including pseudoaneurysms. In our study CT severity index (CTSI) > 7 at admission did not correlate well with organ failure or mortality (p=NS), although the percentage of necrosis had significant correlation with organ failure. Our results are similar to many studies reported in the literature. Simchuk et al. (29) performed a study on 268 patients with acute pancreatitis. They concluded CTSI > 5 correlated significantly with death. Similar results were also obtained by Leung et al. (30) on 121 patients studied retrospectively, and they concluded that CTSI is superior to Ranson’s score and APACHE II score in predicting outcome in pancreatitis. However a few studies found no association between grade of necrosis and outcome of pancreatitis. Shinzeki et al. (31) did not find any correlation between necrosis evident on CECT at admission and outcome of SAP (p=0.061). Another study by Lankisch et al. (32) also did not find any correlation between necrosis and organ failure.

In our study pulmonary and renal were the most common organ failures observed (32% each). The total number of organ failures at admission was also significantly different in both groups (p=0.001), however none of the organ failures independently proved to be a significant predictor of mortality. MMOFS difference was found to be highly significantly correlated with organ failures and outcome. Among the 13 deaths reported in our study, 46.2 % were in the early (<7 days) OF group compared to the late (>7 days) OF group (20%). Our series also showed comparable results with other studies suggesting that early organ failure is the major predictor of poor outcome MMOFS difference was found to be highly significantly (ANOVA, p<0.001 each) correlated with organ failures and outcome. In our study no deaths occurred in the transient OF groups (early transient, late transient and transient deteriorating). We attributed this to the dynamics that transient OF could resolve with treatment and had a better outcome than persistent OF. Among the 13 deaths reported in our study, 46.2 % were in the early (<7 days) OF group compared to the late (>7 days) OF group (20%). Our series also showed comparable results with other studies suggesting that early organ failure is the major predictor of poor outcome (p=0.002) compared to late organ failure (p=0.400).

We found that early persistent OF had a 66.6% mortality as compared to persistent deteriorating organ failure which also had a very high mortality (72.2%). Very few studies have reported on the dynamics of OF with MMOFS. Johnson et al. (19) in a study of 290 patients with SAP had 116 patients with no OF and 147 patients with OF at the time of admission subdivided those with OF into those with persistent (OF lasting for>48 hours) and transient (OF lasting for<48hours) organ failure. Mortality was 36.3% in persistent and 5% in transient OF group. No patients without OF died.

On analysis of the 13 patients who expired, 4 patients died early (<7 days) and 9 deaths were late (>7 days). OF was the main cause of death in both groups, however all patients with sepsis died later. In the study of Yang et al. (33) the most important and common cause of death for patients with fulminant pancreatitis was multiple organ dysfunction syndrome, which usually was the consequence of systemic inflammation response syndrome in the early stage, and severe infection in the later stage, respectively.

Conclusions

Patients with persistent organ failure have a higher mortality. Early persisting and deteriorating organ failure had the worst outcome of among patients with acute pancreatitis. There was an increase in mortality with increasing number of organs involved. The extent of necrosis was directly related with the incidence of organ failure.

References

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Reference as: Maheshwari N, Kumar A, Iqbal ZA, Mandal AK, Vyas A, Wig JD. Organ failure in acute pancreatitis and its impact on outcome in critical care. Southwest J Pulm Crit Care. 2015;10(5):253-64. doi: http://dx.doi.org/10.13175/swjpcc055-15 PDF

Ultrasound for Critical Care Physicians: Tiny Bubbles

Kashif Aslam, MD

Michel Boivin, MD

Division of Pulmonary, Critical care and Sleep Medicine

University of New Mexico School of Medicine

Albuquerque, NM

A 59 year old woman with a past medical history significant for stage IV MALT lymphoma (after chemotherapy and in remission) presented from a long term care facility for respiratory distress and altered mental status. The patient was in hypercarbic respiratory failure with a severe lactic acidosis. Her blood pressure deteriorated, she was begun on vasopressors and intubated.  Pertinent labs demonstrated a white blood cell count of 0.9 X10⁶ /ml, a hemoglobin of 7.1 g/dl, and a platelet count 66 X10⁶  /ml. The patient was started on Cefepime and Linezolid presumptively for septic shock. Ultrasounds of her thorax were performed (Videos 1 & 2).

Video 1.  Ultrasound of the right thorax in the mid-axillary line. 

 

Video 2.  Ultrasound of the right thorax in the mid-axillary line (slightly more caudad).

What is the best explanation for the ultrasound findings shown above? (Click on the correct answer for an explanation)

1. Large pleural effusion
2. Pneumothorax
3. Consolidation due to pneumonia
4. Ruptured diaphragm
5. Lung abscess

Reference as: Aslam K, Boivin M. Ultrasound for critical care physicians: tiny bubbles. Southwest J Pulm Crit Care. 2015;10(5):216-9. doi: http://dx.doi.org/10.13175/swjpcc067-15 PDF

May 2015 Critical Care Case of the Month: An Infected Leg

Sandra L. Till DO and Robert A. Raschke MD

Banner University Good Samaritan Medical Center

Phoenix, AZ

History of Present Illness

A 46-year-old transferred due to concern for necrotizing fasciitis. One the day prior to transfer purple discoloration was not noted in the lower portion of the left leg. On the day of transfer the leg became more purple, painful, and swollen. She presented to a pain clinic that advised her to go to an emergency room. The emergency room performed arterial Doppler ultrasound, which was normal and transferred her due to concern of necrotizing fasciitis.

Past Medical History, Social History and Family History

She has a past medical history of fibromyalgia. She had an extensive surgical history including an appendectomy, bladder implant, cholecystectomy, dilatation and curettage, esophageal repair, left femoral artery repair due to a motor vehicle accident, partial hysterectomy, left knee surgery, and several left leg operations with grafting. Family history was non-contributory. The patient was single with two children, and smoked 1-2 packs of cigarettes per day for 30 years. She denied any illicit drugs or alcohol abuse.

Medications

• Zolpidem
• Warfarin
• Furosemide
• Potassium Chloride
• Morphine sulfate
• Gabapentin
• Oxycodone
• Alprazolam
• Ondansetron
• Amitriptyline

Physical Examination

Vitals signs: Blood pressure 128/85 mm Hg, pulse 86 beat/min, respiratory rate 12, temperature 36.7º C, SPO2 96% on 2L/min of oxygen.

General: Non-toxic, alert and oriented x3, tearful due to pain.

The remainder of the physical examination was unremarkable except for the left lower extremity (Figure 1).

Figure 1. Photograph of the patient's left leg.

Which of the following are appropriate at this time? (Click on the correct answer to proceed to the second of five panels)

1. Blood cultures
2. Complete blood count, c-reactive protein, sodium, creatinine and glucose
3. Surgery consult
4. Wound culture
5. All of the above

Reference as: Till SL, Raschke RA. May 2015 critical care case of the month: an infected leg. Southwest J Pulm Crit Care. 2015;10(5):208-15. doi: http://dx.doi.org/10.13175/swjpcc045-15 PDF