Need of physical and chemical restraints: Experiences at inpatient psychiatric ward in a tertiary care hospital in Karachi, Pakistan

In psychiatry, agitated / aggressive patients are often treated with de-escalation techniques. If this does not work, physical or chemical restrains are required; but in the event of resistance, seclusion is applied. We report the findings of baseline study of experiences of physical and chemical restraints in a tertiary care hospital in Karachi, where 104 files were evaluated retrospectively. The mean age of patients was 32.5 ±14.3 years with 54.8% men, while the average length of stay was 11.5 ±9.3 days. Agitation, violent behaviour, and aggression were the most common indications for restraints. In total, 94.5% of patients had both physical and chemical restraints with the latter being used as the first choice in 70 patients; whereas, 67.1% of patients\u27 families were not informed before application of restraints. The seclusion need assessment was conducted in 4.1% of patients

The role of the cannabinoid system in sepsis

There is growing evidence for an involvement of the cannabinoid system in the pathogenesis of sepsis. In-vitro, immune cell activation increases endocannabinoid release and reduces metabolic breakdown. The net result of this increased endocannabinoid activity may contribute to some of the cardiovascular changes seen in sepsis. In this thesis studies investigating the effects of sepsis on the human immunological-endocannabinoid system are described, first using an in-vitro model of sepsis and secondly in patients admitted to Intensive Care with a diagnosis of sepsis. Q-PCR and mass spectrometry technology were employed to measure receptor mRNA expression and lipid concentrations respectively. In the in-vitro model using polymorphonuclear cells from healthy volunteers, non-stimulated cells expressed mRNA for CB2, CB1 and the controversial third cannabinoid receptor (GPR55). Moreover, a septic stimulus (lipopolysaccharide) caused endocannabinoid and entourage lipid release, along with marked upregulation of CB2 and GPR55 mRNA expression. In the clinical study, the concentrations of some endocannabinoids were increased in patients with sepsis compared to samples taken after recovery. However, lower anandamide and oleoylethanolamide concentrations were associated with increased needs for therapeutic medical interventions (vasoconstrictor drugs, renal replacement therapy and invasive ventilation). These data suggest that endocannabinoids produced by immunocytes may be protective during sepsis. Higher concentrations of endocannabinoids were associated with less cardiovascular instability, renal dysfunction and requirement for invasive ventilation. This might be explained by the anti-inflammatory effects of endocannabinoids. Together, these data support the development of a cannabinoid drug with anti-inflammatory, analgesic and anxiolytic properties as a potential adjunctive treatment for patients with sepsis

The Nociceptin/Orphanin FQ System Is Modulated in Patients Admitted to ICU with Sepsis and after Cardiopulmonary Bypass

BACKGROUND AND OBJECTIVES: Nociceptin/Orphanin FQ (N/OFQ) is a non-classical endogenous opioid peptide that modulates immune function in vitro. Its importance in inflammation and human sepsis is unknown. The objectives of this study were to determine the relationship between N/OFQ, transcripts for its precursor (pre-pro-N/OFQ [ppNOC]) and receptor (NOP), inflammatory markers and clinical outcomes in patients undergoing cardiopulmonary bypass and with sepsis. METHODS: A prospective observational cohort study of 82 patients admitted to Intensive Care (ICU) with sepsis and 40 patients undergoing cardiac surgery under cardiopulmonary bypass (as a model of systemic inflammation). Sixty three healthy volunteers, matched by age and sex to the patients with sepsis were also studied. Clinical and laboratory details were recorded. Polymorph ppNOC and NOP receptor mRNA were determined using quantitative PCR. Plasma N/OFQ was determined using ELISA and cytokines (TNF- α, IL-8, IL-10) measured using radioimmunoassay. Data from patients undergoing cardiac surgery were recorded before, 3 and 24 hours after cardiopulmonary bypass. ICU patients with sepsis were assessed on Days 1 and 2 of ICU admission, and after clinical recovery. MAIN RESULTS: Plasma N/OFQ concentrations increased (p<0.0001) on Days 1 and 2 of ICU admission with sepsis compared to matched recovery samples. Polymorph ppNOC (p= 0.019) and NOP mRNA (p<0.0001) decreased compared to healthy volunteers. TNF-α, IL-8 and IL-10 concentrations increased on Day 1 compared to matched recovery samples and volunteers (p<0.0001). Similar changes (increased plasma N/OFQ, [p=0.0058], decreased ppNOC [p<0.0001], increased IL-8 and IL-10 concentrations [both p<0.0001]) occurred after cardiac surgery but these were comparatively lower and of shorter duration. CONCLUSIONS: The N/OFQ system is modulated in ICU patients with sepsis with similar but reduced changes after cardiac surgery under cardiopulmonary bypass. Further studies are required to clarify the role of the N/OFQ system in inflammation and sepsis, and the mechanisms involved

Study recruitment diagram: cardiac surgical patients.

<p>Study recruitment diagram: cardiac surgical patients.</p

Study recruitment diagram: patients admitted to ICU with sepsis and matched volunteers.

<p>Study recruitment diagram: patients admitted to ICU with sepsis and matched volunteers.</p

Effects of cardiopulmonary bypass on NOP (A) and ppNOC (B) mRNA, N/OFQ peptide (C) concentrations.

<div><p>Panel D represents fold change relative to pre bypass sample. Samples from 40 patients taken immediately before, (t=0), 3h (t=3) and 24h (t=24) hours after the start of cardiopulmonary bypass. A fold change summary is presented in D where it can be seen that following bypass there was a reduction in ppNOC mRNA and an associated increase in N/OFQ. Data presented as median, interquartile and full range and for PCR are presented as change in PCR cycle threshold relative to the geometric mean of the two housekeepers used (ΔCt). Higher ΔCt values indicate more PCR cycles are required to detect the mRNA, and therefore less mRNA is being expressed. For NOP, in 2 samples there was insufficient material for analysis at t=24h. For ppNOC PCR 6 samples at t=0, 4 samples at t=3h and 6 samples at t=24 failed to amplify and there was insufficient material for analysis of a further 2 samples at t=24. Plasma N/OFQ measurements were made in samples from all patients at all time points (n=120), but for 5 samples at t=0, 4 samples at t=3h and 3 samples at t=24h, measurements were set at the lower limit of detection (1.25pg mL^-1). Data were analyzed using Kruskal-Wallis analysis of variance followed by Dunn’s post-hoc testing; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076682#pone-0076682-g004" target="_blank">Figure 4 A-C</a>: There was no change in mRNA expression for the N/OFQ receptor NOP up to 24 hours after cardiac surgery (panels A andD). However, there was a significant decrease (increased ΔCt) in mRNA for the N/OFQ precursor, ppNOC at 3 hours after the onset of cardiopulmonary bypass, which persisted at 24 hours (p<0.0001, panels B and D). This was associated with a significant (35%) increase in N/OFQ at 3h (p=0.0058) that returned to basal values at 24h (panels C and D).</p> <p>*significantly increased compared to t=0. Figure 4D: * significantly different from t=0.</p></div

Effects of sepsis on NOP mRNA, (panel A) and ppNOC (panel B) mRNA, and N/OFQ (panel C) concentrations.

<div><p>Panel D represents fold change relative to recovery samples. Data are median, interquartile and full range and for PCR are presented as change in PCR cycle threshold relative to the geometric man of the two housekeepers used (ΔCT). Higher ΔCT values indicate more PCR cycles are required to detect the mRNA, and therefore less mRNA is being expressed. For NOP PCR samples on Day 1, in 1 sample there was no polymorph prep and one failed to amplify; for Day 2 samples there was no polymorph prep in 4 samples and 2 failed to amplify; for recovery samples there was no polymorph prep in 2 and 4 failed to amplify. For ppNOC PCR on Day 1, in one sample there was no polymorph prep and in 12 there was no amplification; for Day 2 samples there was no polymorph prep in 4 and no amplification in 10; for recovery data there was no polymorph prep in 4 and no amplification in 3; for the volunteer group 16 failed to amplify. Plasma N/OFQ measurements were made in all samples but in the volunteer group 3 samples were set at the limit of detection (1.25pg mL^-1). Data were analyzed using Kruskal-Wallis analysis of variance followed by Dunn’s post-hoc testing; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076682#pone-0076682-g003" target="_blank">Figure 3 A-D</a>: NOP (p<0.001) and ppNOC (p=0.019) mRNA values were lower in patients with sepsis when compared to volunteers and this was more pronounced during the first day in ICU (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076682#pone-0076682-g003" target="_blank">Figure 3</a>, panels A and B). Plasma N/OFQ concentrations were higher on Days 1 & 2 of ICU admission compared to the recovery sample (p<0.0001, panels C and D). N/OFQ concentrations in recovery samples were reduced compared to volunteers (p<0.0001).</p> <p>*significantly different compared to volunteer; † significantly different compared to recovery samples.</p></div